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2019 Volume 47 Issue 10
2019, 47(10): 1443-1454
doi: 10.19756/j.issn.0253-3820.191467
Abstract:
Brain science has become one of the most advanced interdisciplinary research topics. Analysis of brain neurochemistry has attracted great attention in both neuroscience and chemistry, because it provides a powerful tool to understand the physiological and pathological progresses of the brain at a molecular level. For neurochemical monitoring, electrochemical methods come to prominence with high selectivity, sensitivity, spatiotemporal resolution and designable electrode/solution interface to match the pursuit for in vivo analysis of brain neurochemistry. This review summarizes the development of electrochemical approaches toward brain neurochemistry research from both principal and practical perspectives. In addition, future trends of in vivo electrochemical analysis are prospected.
Brain science has become one of the most advanced interdisciplinary research topics. Analysis of brain neurochemistry has attracted great attention in both neuroscience and chemistry, because it provides a powerful tool to understand the physiological and pathological progresses of the brain at a molecular level. For neurochemical monitoring, electrochemical methods come to prominence with high selectivity, sensitivity, spatiotemporal resolution and designable electrode/solution interface to match the pursuit for in vivo analysis of brain neurochemistry. This review summarizes the development of electrochemical approaches toward brain neurochemistry research from both principal and practical perspectives. In addition, future trends of in vivo electrochemical analysis are prospected.
2019, 47(10): 1455-1465
doi: 10.19756/j.issn.0253-3820.191430
Abstract:
The human brain contains about 80 billion nerve cells, and the connections between neurons form a complicated brain neural network. To study the function of the brain mechanisms and the coding principle of the neural network, an important method is to record single-neuron activity as much as possible at the same time. Implantable multichannel neural microelectrodes is a key device that multiple discharge activities of single neurons and can record the spike potential signal of neurons in real-time. In terms of the temporal resolution of neural signals, microelectrode has irreplaceable advantages over other neuroimaging techniques. How to implant more electrodes with more channels in the brain without affecting the function of the brain requires constant innovation and optimization in the material, structure, integration mode and packaging method of implanting multichannel electrodes. This paper briefly reviews the development history of multichannel microwire technology and focuses on the development history, research status and future development trend of implantable multichannel microelectrode by micromachining technology.
The human brain contains about 80 billion nerve cells, and the connections between neurons form a complicated brain neural network. To study the function of the brain mechanisms and the coding principle of the neural network, an important method is to record single-neuron activity as much as possible at the same time. Implantable multichannel neural microelectrodes is a key device that multiple discharge activities of single neurons and can record the spike potential signal of neurons in real-time. In terms of the temporal resolution of neural signals, microelectrode has irreplaceable advantages over other neuroimaging techniques. How to implant more electrodes with more channels in the brain without affecting the function of the brain requires constant innovation and optimization in the material, structure, integration mode and packaging method of implanting multichannel electrodes. This paper briefly reviews the development history of multichannel microwire technology and focuses on the development history, research status and future development trend of implantable multichannel microelectrode by micromachining technology.
2019, 47(10): 1466-1479
doi: 10.19756/j.issn.0253-3820.191465
Abstract:
As the chemical species build the essential basis for mediating and modulating neurotransmission that determines various physiological and pathological states of the central nervous system (CNS), the fundamental research on neurochemistry, especially the investigation of the correlation between neurochemical dynamics and activities of vesicles, single cells, neural circuits and the entire brain, has attracted increasing attention due to its significance in understanding the brain function. Electrochemical analytical methods have made tremendous achievements for in vivo and online continuous monitoring of neurotransmitters and neuromodulators. Among them, the methods utilizing enzymes or aptamers as the biorecognition elements and rationally designing electrode surfaces/interfaces to construct the electrochemical biosensors with high selectivity and high sensitivity undoubtedly provide attractive approaches to quantitative monitoring of brain chemistry. This review mainly focuses on the recent advances in electrochemical biosensors for in vivo analysis.
As the chemical species build the essential basis for mediating and modulating neurotransmission that determines various physiological and pathological states of the central nervous system (CNS), the fundamental research on neurochemistry, especially the investigation of the correlation between neurochemical dynamics and activities of vesicles, single cells, neural circuits and the entire brain, has attracted increasing attention due to its significance in understanding the brain function. Electrochemical analytical methods have made tremendous achievements for in vivo and online continuous monitoring of neurotransmitters and neuromodulators. Among them, the methods utilizing enzymes or aptamers as the biorecognition elements and rationally designing electrode surfaces/interfaces to construct the electrochemical biosensors with high selectivity and high sensitivity undoubtedly provide attractive approaches to quantitative monitoring of brain chemistry. This review mainly focuses on the recent advances in electrochemical biosensors for in vivo analysis.
2019, 47(10): 1480-1491
doi: 10.19756/j.issn.0253-3820.191474
Abstract:
In the central nervous system, the realization of brain functions cannot be achieved without the participation of many ions, therefore, it is of great significance to real-time monitor the dynamic of ions in the living brain for understanding many physiological and pathological events. As a kind of electrochemical sensor, ion-selective electrode has been widely used for in vivo analysis and other fields in the past half century due to its low cost, simple operation and low energy consumption. This review mainly focuses on the development of ion-selective electrodes, and introduces its basic structure and application in the field of brain neurochemical analysis.
In the central nervous system, the realization of brain functions cannot be achieved without the participation of many ions, therefore, it is of great significance to real-time monitor the dynamic of ions in the living brain for understanding many physiological and pathological events. As a kind of electrochemical sensor, ion-selective electrode has been widely used for in vivo analysis and other fields in the past half century due to its low cost, simple operation and low energy consumption. This review mainly focuses on the development of ion-selective electrodes, and introduces its basic structure and application in the field of brain neurochemical analysis.
2019, 47(10): 1492-1501
doi: 10.19756/j.issn.0253-3820.191438
Abstract:
Alzheimer's disease (AD) has attracted extensive attention because it is a fatal and irreversible progressive neurological disorder and its incidence exponentially increases with age. The early diagnosis of AD has become an urgent prerequisite for its treatment. At present, one of the most important biomarkers for the early diagnosis of AD is amyloid-β peptides (Aβ). Owing to the advantages of electrochemical detection, lots of electrochemical biosensors have been developed for detection of Aβ. In the present review, from the standpoint of Aβ bioreceptors, we summarize the progresses in the electrochemical sensors for detection of Aβ monomers, Aβ oligomers and Aβ fibrils, respectively in the recent five years.
Alzheimer's disease (AD) has attracted extensive attention because it is a fatal and irreversible progressive neurological disorder and its incidence exponentially increases with age. The early diagnosis of AD has become an urgent prerequisite for its treatment. At present, one of the most important biomarkers for the early diagnosis of AD is amyloid-β peptides (Aβ). Owing to the advantages of electrochemical detection, lots of electrochemical biosensors have been developed for detection of Aβ. In the present review, from the standpoint of Aβ bioreceptors, we summarize the progresses in the electrochemical sensors for detection of Aβ monomers, Aβ oligomers and Aβ fibrils, respectively in the recent five years.
2019, 47(10): 1502-1511
doi: 10.19756/j.issn.0253-3820.191443
Abstract:
Brain science has attracted more and more attention in the world recently. The storage, release and their function of chemical transmitters are important in neural biology. As the main subcellular organelle for chemical transmitter storage and release, nerve vesicles have attracted much attention. Compared with common vesicle analysis techniques, electroanalytical chemistry has advantages in the analysis of single nerve vesicle due to its high time resolution and sensitivity, especially the use of micro and nano electrodes. In recent years, vesicle impact electrochemical cytometry (VIEC) and resistive-pulse method have been applied rapidly in the field of single vesicles analysis. VIEC can be used to quantitate the storage of neurotransmitters in single vesicles by breaking the vesicle membrane on the electrode surface through electroporation. Resistive-pulse method can be used to measure the size, surface charge, and other parameters or characteristics of vesicles by monitoring the changes of ion current caused by single vesicles passing through micro/nanopores. Focusing on the electro-analysis of single nerve vesicles, this paper mainly introduces the important progress of VIEC and resistive-pulse method in the field of single vesicles analysis in recent years, and has a briefly outlook of the application of these two methods in life analytical chemistry including neuro-analytical chemistry and biomedicine.
Brain science has attracted more and more attention in the world recently. The storage, release and their function of chemical transmitters are important in neural biology. As the main subcellular organelle for chemical transmitter storage and release, nerve vesicles have attracted much attention. Compared with common vesicle analysis techniques, electroanalytical chemistry has advantages in the analysis of single nerve vesicle due to its high time resolution and sensitivity, especially the use of micro and nano electrodes. In recent years, vesicle impact electrochemical cytometry (VIEC) and resistive-pulse method have been applied rapidly in the field of single vesicles analysis. VIEC can be used to quantitate the storage of neurotransmitters in single vesicles by breaking the vesicle membrane on the electrode surface through electroporation. Resistive-pulse method can be used to measure the size, surface charge, and other parameters or characteristics of vesicles by monitoring the changes of ion current caused by single vesicles passing through micro/nanopores. Focusing on the electro-analysis of single nerve vesicles, this paper mainly introduces the important progress of VIEC and resistive-pulse method in the field of single vesicles analysis in recent years, and has a briefly outlook of the application of these two methods in life analytical chemistry including neuro-analytical chemistry and biomedicine.
2019, 47(10): 1512-1523
doi: 10.19756/j.issn.0253-3820.191468
Abstract:
Extracellular space (ECS) is the fluid-filled space surrounding the brain cells, accounting for about one fifth of brain volume. As an essential living environment for neurons and glial cells, ECS not only transports substances for cells, but also enables stable electrical signaling. Therefore, it is closely related to the basic functions of the brain, such as synaptic transmission, memory, sleep and diseases. This review focuses on the primary biophysical characteristics of ECS and the main progress on investigating volume fraction and tortuosity with electrochemical analysis and imaging methods. The review also expounds on the variation of ECS in physiological and pathological processes.
Extracellular space (ECS) is the fluid-filled space surrounding the brain cells, accounting for about one fifth of brain volume. As an essential living environment for neurons and glial cells, ECS not only transports substances for cells, but also enables stable electrical signaling. Therefore, it is closely related to the basic functions of the brain, such as synaptic transmission, memory, sleep and diseases. This review focuses on the primary biophysical characteristics of ECS and the main progress on investigating volume fraction and tortuosity with electrochemical analysis and imaging methods. The review also expounds on the variation of ECS in physiological and pathological processes.
2019, 47(10): 1524-1536
doi: 10.19756/j.issn.0253-3820.191489
Abstract:
β-Amyloid (Aβ) plaques as one of the important pathological hallmarks of Alzheimer's disease (AD) are regarded as key target for diagnosis of AD in early stage. In recent years, near-infrared fluorescence (NIRF) imaging has been developed rapidly, and has become a remarkable, noninvasive and inexpensive optical imaging tool for in vitro biological analysis, in vivo diagnosis and drug screening in animal models. In this review, we summarize current NIRF Aβ probes with sensing mechanism based on the intramolecular charge transfer (ICT) and outlined the influence of chemical structures on optical and biological properties, which is important for further development of high-sensitivity NIRF Aβ probes.
β-Amyloid (Aβ) plaques as one of the important pathological hallmarks of Alzheimer's disease (AD) are regarded as key target for diagnosis of AD in early stage. In recent years, near-infrared fluorescence (NIRF) imaging has been developed rapidly, and has become a remarkable, noninvasive and inexpensive optical imaging tool for in vitro biological analysis, in vivo diagnosis and drug screening in animal models. In this review, we summarize current NIRF Aβ probes with sensing mechanism based on the intramolecular charge transfer (ICT) and outlined the influence of chemical structures on optical and biological properties, which is important for further development of high-sensitivity NIRF Aβ probes.
2019, 47(10): 1537-1548
doi: 10.19756/j.issn.0253-3820.191408
Abstract:
Brain possesses a unique chemical composition and reactivity. Bioactive molecules in brains including metal ions, reactive oxygen species, neurotransmitters and neurotransmitter hydrolases play multifarious and pivotal roles in the function of brain. These molecules keep steady-state concentrations for maintaining the structure and function of brain. However, the abnormal changes at bioactive molecular levels are associated with various brain diseases such as Parkinson's disease, Alzheimer's disease, depression, and so on. Therefore, to explore the concentration and regulation of those molecules in brains is particularly essential for revealing the mysteries of brains and understanding the occurrence and development of brain diseases. Fluorescence imaging is a powerful tool to track bioactive molecules in neurons and in brain because of its remarkable advantages, such as high temporal-spatial resolution, excellent biocompatibility and high sensitivity. In recent years, with the development of fluorescence imaging technology, a variety of fluorescent probes for brain and neurons imaging have been reported. In this review, we summarized the progress of molecular probes, nanoprobes and protein probes for detection of bioactive molecules in neurons and in brain. Furthermore, future research for fluorescence imaging was prospected.
Brain possesses a unique chemical composition and reactivity. Bioactive molecules in brains including metal ions, reactive oxygen species, neurotransmitters and neurotransmitter hydrolases play multifarious and pivotal roles in the function of brain. These molecules keep steady-state concentrations for maintaining the structure and function of brain. However, the abnormal changes at bioactive molecular levels are associated with various brain diseases such as Parkinson's disease, Alzheimer's disease, depression, and so on. Therefore, to explore the concentration and regulation of those molecules in brains is particularly essential for revealing the mysteries of brains and understanding the occurrence and development of brain diseases. Fluorescence imaging is a powerful tool to track bioactive molecules in neurons and in brain because of its remarkable advantages, such as high temporal-spatial resolution, excellent biocompatibility and high sensitivity. In recent years, with the development of fluorescence imaging technology, a variety of fluorescent probes for brain and neurons imaging have been reported. In this review, we summarized the progress of molecular probes, nanoprobes and protein probes for detection of bioactive molecules in neurons and in brain. Furthermore, future research for fluorescence imaging was prospected.
2019, 47(10): 1549-1558
doi: 10.19756/j.issn.0253-3820.191411
Abstract:
Implantable electronics are essential for electrophysiological recording at single-neuron and sub-millisecond resolution in the fields of neuroscience and neuroprosthesis. Advances in nano/microfabrication techniques offer new and exciting opportunities for the development of high-density implantable electronics. However, the mechanical mismatch between microfabricated rigid electronics and soft brain tissues has been shown to cause inflammatory responses, leading to signal degradation during chronic recording. Recently, flexible electronics with improved mechanical compatibility to brain tissues have been intensively investigated to improve the performance of chronic neural recordings. Flexible electronics can form conformal interfaces with brain tissue, resulting in minimized inflammatory responses and stable signal recordings. In addition, ultra-small, high-density, and multiple-functionality are also desirable features of flexible neural electronics. In this review, we highlight recent progress in microfabricated flexible electronics for in vivo brain activity recordings, with a focus on structural design, brain/tissue interface, implantation method, minimization and multifunctional integration.
Implantable electronics are essential for electrophysiological recording at single-neuron and sub-millisecond resolution in the fields of neuroscience and neuroprosthesis. Advances in nano/microfabrication techniques offer new and exciting opportunities for the development of high-density implantable electronics. However, the mechanical mismatch between microfabricated rigid electronics and soft brain tissues has been shown to cause inflammatory responses, leading to signal degradation during chronic recording. Recently, flexible electronics with improved mechanical compatibility to brain tissues have been intensively investigated to improve the performance of chronic neural recordings. Flexible electronics can form conformal interfaces with brain tissue, resulting in minimized inflammatory responses and stable signal recordings. In addition, ultra-small, high-density, and multiple-functionality are also desirable features of flexible neural electronics. In this review, we highlight recent progress in microfabricated flexible electronics for in vivo brain activity recordings, with a focus on structural design, brain/tissue interface, implantation method, minimization and multifunctional integration.
2019, 47(10): 1559-1571
doi: 10.19756/j.issn.0253-3820.191463
Abstract:
Vitamin C, also known as ascorbic acid, is an important neurochemicals in the brain. It serves as one of most important small-molecular-weight antioxidants for neuro-protection and neuromodulator to modulate neurological functions through glutamatergic, dopaminergic and neurotransmission. It is also a cofactor of enzymes involved in biosynthetic reactions such as the synthesis of catecholamines. Therefore, increasing interest has attracted in the measurement of AA in the brain. The high-potential oxidation of AA essentially renders difficulties in exploring the electrochemical property of AA to constitute an electrochemical protocol for its selective detection of AA with high spatial and temporal resolution in the brain. This review mainly focuses on recent updates on detection of AA by modulating the electron transfer of AA to achieve the high temporal, spatial resolution and selectivity for its detection in the rat brain and single-cell.
Vitamin C, also known as ascorbic acid, is an important neurochemicals in the brain. It serves as one of most important small-molecular-weight antioxidants for neuro-protection and neuromodulator to modulate neurological functions through glutamatergic, dopaminergic and neurotransmission. It is also a cofactor of enzymes involved in biosynthetic reactions such as the synthesis of catecholamines. Therefore, increasing interest has attracted in the measurement of AA in the brain. The high-potential oxidation of AA essentially renders difficulties in exploring the electrochemical property of AA to constitute an electrochemical protocol for its selective detection of AA with high spatial and temporal resolution in the brain. This review mainly focuses on recent updates on detection of AA by modulating the electron transfer of AA to achieve the high temporal, spatial resolution and selectivity for its detection in the rat brain and single-cell.
2019, 47(10): 1572-1579
doi: 10.19756/j.issn.0253-3820.191366
Abstract:
The quantitative analysis for neurochemistry in living biosystems has drawn extensive attention, because the physiological active substance participates in the transmission of information and relates to physiology and pathology in the brain. Hydrogen sulfide (H2S), as the third gasotransmitter, plays a significant role in the neurophysiology and neuropathology in brain. In vivo detection of H2S will greatly promote the molecular mechanism in the physiology and pathology process. However, H2S have strong reducibility and volatility, and its properties are similar to those of sulfhydryl compounds in the brain. Therefore, selective separation and recognition of H2S from sulfhydryl compounds in the brain is the key scientific issue in the detection of H2S. Herein, the design principle and research progress of various types of H2S detection methods in recent year were reviewed, and an outlook for the future of H2S detection method was propected.
The quantitative analysis for neurochemistry in living biosystems has drawn extensive attention, because the physiological active substance participates in the transmission of information and relates to physiology and pathology in the brain. Hydrogen sulfide (H2S), as the third gasotransmitter, plays a significant role in the neurophysiology and neuropathology in brain. In vivo detection of H2S will greatly promote the molecular mechanism in the physiology and pathology process. However, H2S have strong reducibility and volatility, and its properties are similar to those of sulfhydryl compounds in the brain. Therefore, selective separation and recognition of H2S from sulfhydryl compounds in the brain is the key scientific issue in the detection of H2S. Herein, the design principle and research progress of various types of H2S detection methods in recent year were reviewed, and an outlook for the future of H2S detection method was propected.
2019, 47(10): 1580-1591
doi: 10.19756/j.issn.0253-3820.191418
Abstract:
Neurotransmitters play an important regulatory role in organisms as endogenous compounds. Accurate determination of neurotransmitters in biological samples is of great significance in early diagnosis of diseases, drug development, basic medical research and other fields. However, it is difficult to achieve accurate analysis because of their complex matrix composition and extremely low concentrations. Therefore, the key to improve the sensitivity and accuracy for the analysis of trace neurotransmitters in complex biological samples is to develop efficient sample pretreatment technology. Microextraction technology is a green extraction technology based on microscale enrichment media which is considered as an excellent pretreatment technology for the analysis of endogenous substances in biological samples due to its low cost, convenient use, adaptability to nondestructive analysis and environmental friendliness. In this paper, we systematically reviewed the application of solid-phase microextraction, micro-solid-phase extraction, and liquid phase microextraction technologies in the high-efficiency enrichment and analysis of trace neurotransmitters in biological samples.
Neurotransmitters play an important regulatory role in organisms as endogenous compounds. Accurate determination of neurotransmitters in biological samples is of great significance in early diagnosis of diseases, drug development, basic medical research and other fields. However, it is difficult to achieve accurate analysis because of their complex matrix composition and extremely low concentrations. Therefore, the key to improve the sensitivity and accuracy for the analysis of trace neurotransmitters in complex biological samples is to develop efficient sample pretreatment technology. Microextraction technology is a green extraction technology based on microscale enrichment media which is considered as an excellent pretreatment technology for the analysis of endogenous substances in biological samples due to its low cost, convenient use, adaptability to nondestructive analysis and environmental friendliness. In this paper, we systematically reviewed the application of solid-phase microextraction, micro-solid-phase extraction, and liquid phase microextraction technologies in the high-efficiency enrichment and analysis of trace neurotransmitters in biological samples.
2019, 47(10): 1592-1600
doi: 10.19756/j.issn.0253-3820.191432
Abstract:
Brain is the central organ of the human nervous system with complex functionality and complicated structure. The chemicals in brain play important roles in metabolism and signal transduction. It is a challenge for scientists to characterize and analyze these chemicals due to their diversity in chemical property and concentration. Mass spectrometry imaging as a new technique is able to screen the spatial distribution of various molecules simultaneously without labeling and has been broadly applied in the study of neurodegenerative disease, brain tumor and pharmacokinetic in brain. This review introduces the principle and new technique of mass spectrometry imaging, and focuses on its typical applications in neuroscience published in recent years.
Brain is the central organ of the human nervous system with complex functionality and complicated structure. The chemicals in brain play important roles in metabolism and signal transduction. It is a challenge for scientists to characterize and analyze these chemicals due to their diversity in chemical property and concentration. Mass spectrometry imaging as a new technique is able to screen the spatial distribution of various molecules simultaneously without labeling and has been broadly applied in the study of neurodegenerative disease, brain tumor and pharmacokinetic in brain. This review introduces the principle and new technique of mass spectrometry imaging, and focuses on its typical applications in neuroscience published in recent years.
2019, 47(10): 1601-1611
doi: 10.19756/j.issn.0253-3820.191459
Abstract:
Single-cell assays has emerged as a cutting-edge technique during the past decade. Despite several issues (including pL volume, extremely complicated intracellular fluid and maintaining cell viability during sampling) still need to be addressed, single-cell mass spectrometry for metabolites has achieved remarkable results recently. Various mass spectrometry-based approaches have enabled identification of vast cytoplasmic chemical constituents at single cell level, which greatly facilitate the single neuron analysis at different physiological conditions. In this review, we have concluded recent single-cell mass spectrometry investigations toward single neuron analysis, including single ovum/zygote, single cultured cell, single freshly isolated cell and single cell/neuron on tissue.
Single-cell assays has emerged as a cutting-edge technique during the past decade. Despite several issues (including pL volume, extremely complicated intracellular fluid and maintaining cell viability during sampling) still need to be addressed, single-cell mass spectrometry for metabolites has achieved remarkable results recently. Various mass spectrometry-based approaches have enabled identification of vast cytoplasmic chemical constituents at single cell level, which greatly facilitate the single neuron analysis at different physiological conditions. In this review, we have concluded recent single-cell mass spectrometry investigations toward single neuron analysis, including single ovum/zygote, single cultured cell, single freshly isolated cell and single cell/neuron on tissue.
2019, 47(10): 1612-1621
doi: 10.19756/j.issn.0253-3820.191455
Abstract:
In vivo electrochemistry is one of the attractive approaches for tracking of the dynamic of neurochemicals in the brain. Carbon fiber electrodes (CFE) are usually implanted in specific brain regions for monitoring neurochemicals due to its high spatial and temporal resolution, high sensitivity and small brain tissue damage. However, the implantation of CFE can trigger a series of negative effects for in vivo analysis. On the one hand, protein nonspecific adsorption causes the decrease in electrodes sensitivity. On the other hand, protein-mediated cell adhesion on microelectrode surface can lead to microchemical environment changes around the microelectrode, which affects the accuracy and reliability of the detection results toward neurochemicals. In addition, the resulting fibrous capsule blocks electron transfer between electrode surface and electrolyte, resulting in failure in terms of sensing. In this paper, we briefly introduced the effect of protein adsorption on the electrochemical performance and reviewed the recent advances on antifouling of microelectrode for in vivo electrochemistry.
In vivo electrochemistry is one of the attractive approaches for tracking of the dynamic of neurochemicals in the brain. Carbon fiber electrodes (CFE) are usually implanted in specific brain regions for monitoring neurochemicals due to its high spatial and temporal resolution, high sensitivity and small brain tissue damage. However, the implantation of CFE can trigger a series of negative effects for in vivo analysis. On the one hand, protein nonspecific adsorption causes the decrease in electrodes sensitivity. On the other hand, protein-mediated cell adhesion on microelectrode surface can lead to microchemical environment changes around the microelectrode, which affects the accuracy and reliability of the detection results toward neurochemicals. In addition, the resulting fibrous capsule blocks electron transfer between electrode surface and electrolyte, resulting in failure in terms of sensing. In this paper, we briefly introduced the effect of protein adsorption on the electrochemical performance and reviewed the recent advances on antifouling of microelectrode for in vivo electrochemistry.
2019, 47(10): 1622-1628
doi: 10.19756/j.issn.0253-3820.191421
Abstract:
Alzheimer's disease (AD) is an age-related neurological disorder, affecting millions of people around the world, but the exact cause of the disease remains unclear. Matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) analysis technology not only enables material identification, but also spatially images the analytes. In recent years, MALDI MSI technique has been widely applied to the study of the distribution of β-amyloid (Aβ) and lipid in AD brain tissue. The principle, methodology of MALDI MSI and related research progress of the mechanism of AD treatment were reviewed in this paper, and the prospects for its development were also anticipated.
Alzheimer's disease (AD) is an age-related neurological disorder, affecting millions of people around the world, but the exact cause of the disease remains unclear. Matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) analysis technology not only enables material identification, but also spatially images the analytes. In recent years, MALDI MSI technique has been widely applied to the study of the distribution of β-amyloid (Aβ) and lipid in AD brain tissue. The principle, methodology of MALDI MSI and related research progress of the mechanism of AD treatment were reviewed in this paper, and the prospects for its development were also anticipated.
2019, 47(10): 1629-1638
doi: 10.19756/j.issn.0253-3820.191358
Abstract:
Targeted delivery of molecules and materials across blood-brain barrier (BBB) is critical for in-situ and real-time analysis of central nervous system, which is also a challenge for analytical chemistry. As a kind of endogenous bioactive species, peptides with modulate structure can be designed with predictable conformations and chemically synthesized with high efficiency and purity. Peptides can act as BBB shuttles to transport fluorescent dyes, contrast agents and nanomaterial to target tissues, providing new tools and analytical methods for brain science, disease detection and molecular mechanism investigation. This review summarizes recent advances in analytical applications of BBB shuttle peptides for studying central nervous system. Introduction on BBB, peptides as well as design and screening approaches of BBB shuttle peptides is also included.
Targeted delivery of molecules and materials across blood-brain barrier (BBB) is critical for in-situ and real-time analysis of central nervous system, which is also a challenge for analytical chemistry. As a kind of endogenous bioactive species, peptides with modulate structure can be designed with predictable conformations and chemically synthesized with high efficiency and purity. Peptides can act as BBB shuttles to transport fluorescent dyes, contrast agents and nanomaterial to target tissues, providing new tools and analytical methods for brain science, disease detection and molecular mechanism investigation. This review summarizes recent advances in analytical applications of BBB shuttle peptides for studying central nervous system. Introduction on BBB, peptides as well as design and screening approaches of BBB shuttle peptides is also included.
2019, 47(10): 1639-1650
doi: 10.19756/j.issn.0253-3820.191428
Abstract:
The brain is probably the most complex system. Neurocircuits, formed by various types of neurons through synaptic connections, are the basis of brain functions, from the basic homeostasis, senses and perception, for learning, memory, decision-making, and consciousness. Therefore, it is of great significance to understand the component and working principle of neurocircuits, so as to recognize, utilize and protect the brain. Techniques for exploring the structure and function of neurocircuits include circuit-tracing, manipulating, imaging and data-analyzing. In this paper, we focus on the neurocircuit tracers based on neurotropic viruses and its application technology. The categories and characteristics, genetic modification, selection principles and application limitations of commonly used neurotropic viral tools will be discussed. The non-transsynaptic tracer system, the trans-monosynaptic tracer system and the trans-multisynaptic tracer system are also introduced to help readers understand the commonly used circuit tracing methods and research progress.
The brain is probably the most complex system. Neurocircuits, formed by various types of neurons through synaptic connections, are the basis of brain functions, from the basic homeostasis, senses and perception, for learning, memory, decision-making, and consciousness. Therefore, it is of great significance to understand the component and working principle of neurocircuits, so as to recognize, utilize and protect the brain. Techniques for exploring the structure and function of neurocircuits include circuit-tracing, manipulating, imaging and data-analyzing. In this paper, we focus on the neurocircuit tracers based on neurotropic viruses and its application technology. The categories and characteristics, genetic modification, selection principles and application limitations of commonly used neurotropic viral tools will be discussed. The non-transsynaptic tracer system, the trans-monosynaptic tracer system and the trans-multisynaptic tracer system are also introduced to help readers understand the commonly used circuit tracing methods and research progress.
2019, 47(10): 1651-1663
doi: 10.19756/j.issn.0253-3820.191427
Abstract:
Neurotransmitters are critical molecules for nervous system to transmit and modulate information between neurons and other cell types such as glia cells. Measurement of neurotransmitter concentration in vivo can develop and verify numerous novel biomarkers for identifying neurological disorders such as Parkinson's disease, Alzheimer's disease, post-traumatic stress disorder, epilepsy and schizophrenia etc. Meanwhile, in vivo biosensors for neurotransmitters can facilitate neuroscience research in many aspects, such as understanding the basis of cognition, reward, addiction, aversion, learning and memory, as well as the circuitry mechanisms of various neurological disorders. Whilst the in vitro application of neurotransmitter sensors has improved greatly with the advancement of nano materials, microfluidic devices, multielectrode arrays, and many other techniques, in vivo biosensors have not seen many applications in neuroscience field. This review focuses on recent advancement in biosensing techniques for in vitro and in vivo applications. Some techniques use the potential to improve the detection sensitivity and precision of many diseases, and others may be combined with in vivo electrophysiology, optogenetics for improving neural circuitry research. This review also emphasizes novel materials as components of sensors, such as carbon nanomaterials, conducting polymers, aptamers and metal nano-particles.
Neurotransmitters are critical molecules for nervous system to transmit and modulate information between neurons and other cell types such as glia cells. Measurement of neurotransmitter concentration in vivo can develop and verify numerous novel biomarkers for identifying neurological disorders such as Parkinson's disease, Alzheimer's disease, post-traumatic stress disorder, epilepsy and schizophrenia etc. Meanwhile, in vivo biosensors for neurotransmitters can facilitate neuroscience research in many aspects, such as understanding the basis of cognition, reward, addiction, aversion, learning and memory, as well as the circuitry mechanisms of various neurological disorders. Whilst the in vitro application of neurotransmitter sensors has improved greatly with the advancement of nano materials, microfluidic devices, multielectrode arrays, and many other techniques, in vivo biosensors have not seen many applications in neuroscience field. This review focuses on recent advancement in biosensing techniques for in vitro and in vivo applications. Some techniques use the potential to improve the detection sensitivity and precision of many diseases, and others may be combined with in vivo electrophysiology, optogenetics for improving neural circuitry research. This review also emphasizes novel materials as components of sensors, such as carbon nanomaterials, conducting polymers, aptamers and metal nano-particles.
2019, 47(10): 1664-1670
doi: 10.19756/j.issn.0253-3820.191454
Abstract:
Simultaneous analysis of hydrogen peroxide (H2O2) and dopamine (DA) in the central nervous system is of great significance and has great challenges. Herein, a ring-disk microelectrode for simultaneous electrochemical analysis of H2O2 and DA was developed. To selectively detect H2O2, the carbon fiber disk (CFdisk) electrode in the middle of the ring-disk microelectrode was electrochemically modified by Prussian blue (PB) and poly(2,3-dihydrothieno-1,4-dioxin) (PEDOT). The Auring on the periphery of the ring-disk microelectrode was used to detect DA. The ring-disk microelectrode exhibited sensitive response to H2O2 (linearity range:1-29 μmol/L) and DA (linearity range:0.5-25 μmol/L) with a detection limit of 0.4 μmol/L and 0.18 μmol/L, respectively. The ring-disk microelectrode was successfully used in measuring H2O2 and DA in rat brain. This method provided a new platform for the study of neurophysiology and pathology of H2O2 and DA.
Simultaneous analysis of hydrogen peroxide (H2O2) and dopamine (DA) in the central nervous system is of great significance and has great challenges. Herein, a ring-disk microelectrode for simultaneous electrochemical analysis of H2O2 and DA was developed. To selectively detect H2O2, the carbon fiber disk (CFdisk) electrode in the middle of the ring-disk microelectrode was electrochemically modified by Prussian blue (PB) and poly(2,3-dihydrothieno-1,4-dioxin) (PEDOT). The Auring on the periphery of the ring-disk microelectrode was used to detect DA. The ring-disk microelectrode exhibited sensitive response to H2O2 (linearity range:1-29 μmol/L) and DA (linearity range:0.5-25 μmol/L) with a detection limit of 0.4 μmol/L and 0.18 μmol/L, respectively. The ring-disk microelectrode was successfully used in measuring H2O2 and DA in rat brain. This method provided a new platform for the study of neurophysiology and pathology of H2O2 and DA.
2019, 47(10): 1671-1679
doi: 10.19756/j.issn.0253-3820.191439
Abstract:
In vivo proton magnetic resonance spectroscopy (1H-MRS) can be used to measure regional concentration of multiple brain metabolites simultaneously and non-invasively. The technique has been widely used in the clinical diagnosis and basic researches on neurological/psychiatry diseases. In this study, the concentrations of five cerebral metabolites, namely N-acetyl aspartate (NAA), glutamate (Glu), glutamine (Gln), taurine (Tau) and glutathione (GSH) in two brain regions (i.e., striatum and medial prefrontal cortex) of 12-months old mice were measured by in vivo 1H-MRS using water signal as the internal standard. The detection results were then compared with those obtained by liquid-state 1H-NMR and ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The results demonstrated that the NAA, Glu and Tau concentrations measured by the three techniques had no statistically significant differences among each other, suggesting that the results of in vivo 1H-MRS analyses were at least as reliably and accurate as those obtained by 1H-NMR and UHPLC-MS/MS. The absolute concentrations of Gln and GSH measured by UHPLC-MS/MS were significantly higher or lower, relative to those measured with magnetic resonance techniques. Such discrepancies might have originated from the systematic errors presented in the UHPLC-MS/MS measurements of Gln and GSH. The results demonstrated the feasibility of combined or complementary use of in vivo 1H-MRS and ex vivo measurements for metabolite profiling in the brain.
In vivo proton magnetic resonance spectroscopy (1H-MRS) can be used to measure regional concentration of multiple brain metabolites simultaneously and non-invasively. The technique has been widely used in the clinical diagnosis and basic researches on neurological/psychiatry diseases. In this study, the concentrations of five cerebral metabolites, namely N-acetyl aspartate (NAA), glutamate (Glu), glutamine (Gln), taurine (Tau) and glutathione (GSH) in two brain regions (i.e., striatum and medial prefrontal cortex) of 12-months old mice were measured by in vivo 1H-MRS using water signal as the internal standard. The detection results were then compared with those obtained by liquid-state 1H-NMR and ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The results demonstrated that the NAA, Glu and Tau concentrations measured by the three techniques had no statistically significant differences among each other, suggesting that the results of in vivo 1H-MRS analyses were at least as reliably and accurate as those obtained by 1H-NMR and UHPLC-MS/MS. The absolute concentrations of Gln and GSH measured by UHPLC-MS/MS were significantly higher or lower, relative to those measured with magnetic resonance techniques. Such discrepancies might have originated from the systematic errors presented in the UHPLC-MS/MS measurements of Gln and GSH. The results demonstrated the feasibility of combined or complementary use of in vivo 1H-MRS and ex vivo measurements for metabolite profiling in the brain.
2019, 47(10): 1680-1688
doi: 10.19756/j.issn.0253-3820.191426
Abstract:
Alzheimer's disease (AD) is a major type of dementia in the elderly. Clinical medication at present can only relieve symptoms but has no therapeutical effect. Thus, it is urgent to develop an effective drug for the treatment of AD. In this study, 2-month-old triple transgenic AD model mice (3×Tg-AD) were treated respectively with 0.2 and 1.0 mmol/L bis(ethylmaltolato) oxidovanadium IV (BEOV) in drinking water for 2 months. The open field test, the elevated plus-maze test and the Y maze test were applied to those mice, showing that BEOV could significantly improve the exploratory ability, memory capacity and exercise ability and relieve the anxiety of 4-month-old 3×Tg-AD mice. The dendritic spines of pyramidal neurons in neocortex were detected by in-vivo two-photon imaging of YFP and AD-YFP mice (the offspring of 3×Tg-AD and YFP mice). The numbers of dendritic spines increased in YFP mice but decreased in AD-YFP mice from 2.5-month-old to 3.5-month-old. Treatment with 1.0 mmol/L BEOV in the AD-YFP mice significantly increased the numbers of total dendritic spines, mushroom spines and thin spines, which suggested that BEOV could protect cortical neurons and reduce the loss of dendritic spines. The levels of metal ions in the brain of mice were further measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that 1.0 mmol/L BEOV could significantly increase the levels of V and Se and decrease the levels of Fe, Zn, Hg, Pb, Bi and Ni in AD brains, implying that vanadium might synergize with selenium to regulate the levels of metal ions in AD mice. Summarily, BEOV could mediate the homeostasis of multiple metal ions in AD brain and protect cortical neurons and thus to interfere with the pathological process of AD.
Alzheimer's disease (AD) is a major type of dementia in the elderly. Clinical medication at present can only relieve symptoms but has no therapeutical effect. Thus, it is urgent to develop an effective drug for the treatment of AD. In this study, 2-month-old triple transgenic AD model mice (3×Tg-AD) were treated respectively with 0.2 and 1.0 mmol/L bis(ethylmaltolato) oxidovanadium IV (BEOV) in drinking water for 2 months. The open field test, the elevated plus-maze test and the Y maze test were applied to those mice, showing that BEOV could significantly improve the exploratory ability, memory capacity and exercise ability and relieve the anxiety of 4-month-old 3×Tg-AD mice. The dendritic spines of pyramidal neurons in neocortex were detected by in-vivo two-photon imaging of YFP and AD-YFP mice (the offspring of 3×Tg-AD and YFP mice). The numbers of dendritic spines increased in YFP mice but decreased in AD-YFP mice from 2.5-month-old to 3.5-month-old. Treatment with 1.0 mmol/L BEOV in the AD-YFP mice significantly increased the numbers of total dendritic spines, mushroom spines and thin spines, which suggested that BEOV could protect cortical neurons and reduce the loss of dendritic spines. The levels of metal ions in the brain of mice were further measured by inductively coupled plasma mass spectrometry (ICP-MS). The results showed that 1.0 mmol/L BEOV could significantly increase the levels of V and Se and decrease the levels of Fe, Zn, Hg, Pb, Bi and Ni in AD brains, implying that vanadium might synergize with selenium to regulate the levels of metal ions in AD mice. Summarily, BEOV could mediate the homeostasis of multiple metal ions in AD brain and protect cortical neurons and thus to interfere with the pathological process of AD.
2019, 47(10): 1689-1694
doi: 10.19756/j.issn.0253-3820.191485
Abstract:
Nervous system is a significant command system, and the communication between neurons depends on anterograde messengers such as neurotransmitters released from presynaptic neurons and retrograde messengers from postsynaptic cells. As an important kind of retrograde messengers, nitric oxide can regulate synaptic strength for different physiological needs. Whereas, most current researches focus on presynaptic exocytosis of neurotransmitters but ignore the detection of retrograde messengers. To monitor retrograde messenger nitric oxide released from postsynaptic neurons, we developed an electrochemical sensor with rapid response, high sensitivity and spatio-temporal resolution by modifying platinum nanoparticles on carbon fiber microelectrodes. The ability of hippocampal neurons to synthesize and secrete nitric oxide was firstly evidenced by successful detection of nitric oxide released from L-arginine-or glutamate-stimulated neurons. On this basis, the neuronal transmission was initiated by stimulating presynaptic neuron with high potassium solution, and the nitric oxide released from postsynaptic neurons was monitored in real time. The results demonstrated that synaptic transmission was accompanied with the release of retrograde messengers. This method has promising potential in exploring synaptic feedback regulation and plasticity in nervous system.
Nervous system is a significant command system, and the communication between neurons depends on anterograde messengers such as neurotransmitters released from presynaptic neurons and retrograde messengers from postsynaptic cells. As an important kind of retrograde messengers, nitric oxide can regulate synaptic strength for different physiological needs. Whereas, most current researches focus on presynaptic exocytosis of neurotransmitters but ignore the detection of retrograde messengers. To monitor retrograde messenger nitric oxide released from postsynaptic neurons, we developed an electrochemical sensor with rapid response, high sensitivity and spatio-temporal resolution by modifying platinum nanoparticles on carbon fiber microelectrodes. The ability of hippocampal neurons to synthesize and secrete nitric oxide was firstly evidenced by successful detection of nitric oxide released from L-arginine-or glutamate-stimulated neurons. On this basis, the neuronal transmission was initiated by stimulating presynaptic neuron with high potassium solution, and the nitric oxide released from postsynaptic neurons was monitored in real time. The results demonstrated that synaptic transmission was accompanied with the release of retrograde messengers. This method has promising potential in exploring synaptic feedback regulation and plasticity in nervous system.
2019, 47(10): 1695-1702
doi: 10.19756/j.issn.0253-3820.191437
Abstract:
The reaction process between Ag and I2 was investigated by the localized surface plasmon resonance (LSPR) technique. Au@Ag nanocubes (Au@Ag NCs) were used as a probe to analyze the different color ratio and scattering intensity of the probe and I2 after adding different concentrations of I-/I2 under the dark-field microscopy (DFM). Furthermore, transmission electron microscopy (TEM) and UV-Visible absorption spectra showed that Au@Ag NCs were continuously oxidized from the edges, gradually became spherical, and finally quasi-spherical. Finally, Au@Ag NCs were used as probes to test I2. The detection range was from 0.1 μmol/L to 50 μmol/L with a detection limit of 17 nmol/L. This work laid the foundation for the study of oxidative corrosion between Ag and I2, and also provided a new highly sensitive method for detection of I2 in brain rat dialysate.
The reaction process between Ag and I2 was investigated by the localized surface plasmon resonance (LSPR) technique. Au@Ag nanocubes (Au@Ag NCs) were used as a probe to analyze the different color ratio and scattering intensity of the probe and I2 after adding different concentrations of I-/I2 under the dark-field microscopy (DFM). Furthermore, transmission electron microscopy (TEM) and UV-Visible absorption spectra showed that Au@Ag NCs were continuously oxidized from the edges, gradually became spherical, and finally quasi-spherical. Finally, Au@Ag NCs were used as probes to test I2. The detection range was from 0.1 μmol/L to 50 μmol/L with a detection limit of 17 nmol/L. This work laid the foundation for the study of oxidative corrosion between Ag and I2, and also provided a new highly sensitive method for detection of I2 in brain rat dialysate.
2019, 47(10): 1703-1709
doi: 10.19756/j.issn.0253-3820.191312
Abstract:
Although deep brain stimulation (DBS) has become an effective treatment for improving dyskinesia in Parkinson's disease, the exact treatment mechanism remains unclear. In addition, the current system researching DBS mechanism is always composed of two individual parts:the electrical stimulation instrument and the signal detection instrument, which makes it easy to cause the complicated operation of procedure and the waste of resource. In this work, a comprehensive experimental system was established, including an electrostimulation-detection instrument which integrated the function of electrical stimulation and neural signal detection, and the microelectrode arrays (MEA) which were fabricated by micro-electro-mechanical system (MEMS) and modified by nanoplatinum and nafion membrane. Experimental results showed that dopamine in concentration range of 1-50 μmol/L had a good linear relationship with the surface oxidation current of the modified MEA, and the linear correlation coefficient was 0.998. What's more, DBS was designed with the medial forebrain bundle (MFB) as stimulation target and the striatum as detection area, which made the striatal simultaneous observation of dopamine concentration and neuronal firing was achieved while electrical stimulation was applied. Experimental results indicated that the concentration of dopamine in the striatum increased rapidly after stimulation, reaching a maximum of 2.06 μmol/L which was about 1.57 times of the pre-stimulation level; the spike firing rate increased from 1.17 Hz to 6.77 Hz; and the power of local field potential was enhanced from 0.19 mW to 0.64 mW. The electrostimulation-detection system developed in this study realized the integration of electrical stimulation and dual-mode signal detection, which simplified the complex experimental steps and was expected to provide an effective experimental tool for the exploration of DBS treatment mechanism.
Although deep brain stimulation (DBS) has become an effective treatment for improving dyskinesia in Parkinson's disease, the exact treatment mechanism remains unclear. In addition, the current system researching DBS mechanism is always composed of two individual parts:the electrical stimulation instrument and the signal detection instrument, which makes it easy to cause the complicated operation of procedure and the waste of resource. In this work, a comprehensive experimental system was established, including an electrostimulation-detection instrument which integrated the function of electrical stimulation and neural signal detection, and the microelectrode arrays (MEA) which were fabricated by micro-electro-mechanical system (MEMS) and modified by nanoplatinum and nafion membrane. Experimental results showed that dopamine in concentration range of 1-50 μmol/L had a good linear relationship with the surface oxidation current of the modified MEA, and the linear correlation coefficient was 0.998. What's more, DBS was designed with the medial forebrain bundle (MFB) as stimulation target and the striatum as detection area, which made the striatal simultaneous observation of dopamine concentration and neuronal firing was achieved while electrical stimulation was applied. Experimental results indicated that the concentration of dopamine in the striatum increased rapidly after stimulation, reaching a maximum of 2.06 μmol/L which was about 1.57 times of the pre-stimulation level; the spike firing rate increased from 1.17 Hz to 6.77 Hz; and the power of local field potential was enhanced from 0.19 mW to 0.64 mW. The electrostimulation-detection system developed in this study realized the integration of electrical stimulation and dual-mode signal detection, which simplified the complex experimental steps and was expected to provide an effective experimental tool for the exploration of DBS treatment mechanism.
