Metabolically Active Synaptosomes Can Be Prepared from Frozen Rat and Human Brain

Abstract: Nerve ending particles (synaptosomes) were prepared from pieces of rat and human brain and from brain homogenate that had been frozen and thawed under a variety of conditions. Their purity, as judged by electron microscopy, and performance in terms of a number of metabolic and functional parameters [accumulation of tissue potassium, respiration, release of transmitter amino acids, and the responses on these indices to depolarisation by veratrine (VX)] were compared with those of fresh tissue-derived synaptosomes. It was found that rapid freezing and/or slow thawing severely impaired the subsequent performance of incubated synaptosomes. In contrast, synaptosomes from tissue frozen slowly and thawed rapidly showed relatively good retention of morphology and metabolic performance. It was better to use whole (1-5 g) pieces of tissue than tissue homogenate: the synaptosome fraction from frozen tissue pieces contained 80% of the proportion of identified synaptosomes found in the fresh tissue synaptosome fraction, its respiratory rate was 65%, and its tissue potassium content 70% of that of fresh controls. Moreover, it responded to VX or potassium stimulation by showing increased respiratory rate, decreased tissue potassium, and increased release of neurotransmitter amino acids, to an extent that was comparable to that of fresh tissue fractions. Thus, preparations from frozen rat and human brain were shown to be metabolically and functionally active, and can be used for a variety of neurotransmitter-related studies.     

Models of active transport of neurotransmitters in synaptic vesicles

Models of the active transport of neurotransmitters in synaptic vesicles were constructed. The models were used to determine the resting potential at membranes of synaptic vesicles: 40mV (monoamines and acetylcholine) and -40mV (glutamate). The potential at the membrane of a synaptic vesicle was almost absent for the transport of GABA and glycine. The neurotransmitter concentration of a cell was 0.1-18mM at the concentration of neurotransmitters in a vesicle equal to 0.5M. This result is in qualitative agreement with the relevant experimental data.     

P2X receptors mediated abnormal interaction between satellite glial cells and neurons in visceral pathological changes

The adenosine triphosphate (ATP)‐gated P2X receptor cation channel family consists of permeable ligand‐gated ion channels that expand on the binding of extracellular adenosine 5’‐ATP. ATP‐gated P2X receptors are trimer ion channels that assemble homo or isomer from seven cloned subunits. P2X receptors are discovered mostly in mammalian and are being found in an increasing number of non‐vertebrates, such as zebrafish, bullfrog, and ameba. P2X receptors are involved in many physiological processes, including regulation of heart rhythm and contractility, and regulation of pain, especially chronic pain and glia integration. This review summarizes the current studies on the regulation of P2X receptors in abnormal neuronal‐glial interaction and the pathological changes in viscera, especially in myocardial ischemia.     

Analysis of Plasma Biopterin Levels in Psychiatric Disorders Suggests a Common BH<Subscript>4</Subscript> Deficit in Schizophrenia and Schizoaffective Disorder

Tetrahydrobiopterin (BH₄) is an essential cofactor for amine neurotransmitter synthesis. BH₄ also stimulates and modulates the glutamatergic system, and regulates the synthesis of nitric oxide by nitric oxide synthases. A connection between BH₄ deficiencies and psychiatric disorders has been previously reported; major depression and obsessive-compulsive disorder have been found in subjects with a BH₄ deficiency disorder and more recently we have observed a robust plasma deficit of biopterin (a measure of BH₄), in a large group of schizophrenic patients compared to control subjects. To extend our previous finding in schizophrenia, we analyzed plasma biopterin levels from patients with schizoaffective and bipolar disorders. A significant difference in biopterin was seen among the diagnostic groups (P < 0.0001). Post hoc analyses indicated significant biopterin deficits relative to the normal control group for the schizoaffective group, who had biopterin levels comparable to the schizophrenic group. Bipolar disorder subjects had plasma biopterin levels that were higher that the schizoaffective disorder group and significantly higher than the schizophrenic group. The demonstrated significant biopterin deficit in both schizophrenia and schizoaffective disorder, may suggest an etiological role of a BH₄ deficit in these two disorders, via dysregulation of neurotransmitter systems.     

Should I stay or should I go? How the human brain manages the trade-off between exploitation and exploration

Many large and small decisions we make in our daily lives-which ice cream to choose, what research projects to pursue, which partner to marry-require an exploration of alternatives before committing to and exploiting the benefits of a particular choice. Furthermore, many decisions require re-evaluation, and further exploration of alternatives, in the face of changing needs or circumstances. That is, often our decisions depend on a higher level choice: whether to exploit well known but possibly suboptimal alternatives or to explore risky but potentially more profitable ones. How adaptive agents choose between exploitation and exploration remains an important and open question that has received relatively limited attention in the behavioural and brain sciences. The choice could depend on a number of factors, including the familiarity of the environment, how quickly the environment is likely to change and the relative value of exploiting known sources of reward versus the cost of reducing uncertainty through exploration. There is no known generally optimal solution to the exploration versus exploitation problem, and a solution to the general case may indeed not be possible. However, there have been formal analyses of the optimal policy under constrained circumstances. There have also been specific suggestions of how humans and animals may respond to this problem under particular experimental conditions as well as proposals about the brain mechanisms involved. Here, we provide a brief review of this work, discuss how exploration and exploitation may be mediated in the brain and highlight some promising future directions for research.     

Review: Microbial endocrinology: intersection of microbiology and neurobiology matters to swine health from infection to behavior

From birth to slaughter, pigs are in constant interaction with microorganisms. Exposure of the skin, gastrointestinal and respiratory tracts, and other systems allows microorganisms to affect the developmental trajectory and function of porcine physiology as well as impact behavior. These routes of communication are bi-directional, allowing the swine host to likewise influence microbial survival, function and community composition. Microbial endocrinology is the study of the bi-directional dialogue between host and microbe. Indeed, the landmark discovery of host neuroendocrine systems as hubs of host–microbe communication revealed neurochemicals act as an inter-kingdom evolutionary-based language between microorganism and host. Several such neurochemicals are stress catecholamines, which have been shown to drastically increase host susceptibility to infection and augment virulence of important swine pathogens, including Clostridium perfringens. Catecholamines, the production of which increase in response to stress, reach the epithelium of multiple tissues, including the gastrointestinal tract and lung, where they initiate diverse responses by members of the microbiome as well as transient microorganisms, including pathogens and opportunistic pathogens. Multiple laboratories have confirmed the evolutionary role of microbial endocrinology in infectious disease pathogenesis extending from animals to even plants. More recent investigations have now shown that microbial endocrinology also plays a role in animal behavior through the microbiota–gut–brain axis. As stress and disease are ever-present, intersecting concerns during each stage of swine production, novel strategies utilizing a microbial endocrinology-based approach will likely prove invaluable to the swine industry.     

交感神经系统内递质共存及其相互作用

在外周交感神经系统内,神经递质或神经肽类物质主要存在于大、小囊泡内;递质共存的现象在交感神经内不断得以发现．去甲肾上腺素和乙酰胆碱、神经肽Y、脑啡肽、P物质、血管活性肠肽、生长抑素、神经降压素、降钙素基因相关肽等物质共存的证实,扩大了交感神经递质的调节范围,递质之间网络式的相互调节作用有着重要的生理意义。     

昆虫分子生物学的一些进展：神经递质和离子通道

昆虫分子生物学的一些进展：神经递质和离子通道翟启慧（中国科学院动物研究所北京１０００８０）１神经递质神经递质（ｎｅｕｒｏｔｒａｎ。ｍｉｔｔｅｒ）是在化学突触神经ｆＧ。１问传递信息的化学物质。神经递质有许多不同类型,如乙酸胆碱、丫一氨基丁酸、生物胺等。...     

多囊卵巢综合征并发抑郁症的研究现状

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄女性最常见的内分泌疾病之一,表现为生殖和代谢异常。近些年来,越来越多的人群学研究发现,PCOS病人患精神心理疾病,尤其是抑郁症的发生率高于正常人群。本文概述了PCOS并发抑郁症的相关危险因素和可能机制,并简要论述了PCOS的治疗药物对抑郁症作用的最新研究进展。     

How fast monoamine oxidases decompose adrenaline? Kinetics of isoenzymes A and B evaluated by empirical valence bond simulation

This work scrutinizes kinetics of decomposition of adrenaline catalyzed by monoamine oxidase (MAO) A and B enzymes, a process controlling the levels of adrenaline in the central nervous system and other tissues. Experimental kinetic data for MAO A and B catalyzed decomposition of adrenaline are reported only in the form of the maximum reaction rate. Therefore, we estimated the experimental free energy barriers form the kinetic data of closely related systems using regression method, as was done in our previous study. By using multiscale simulation on the Empirical Valence Bond (EVB) level, we studied the chemical reactivity of the MAO A catalyzed decomposition of adrenaline and we obtained a value of activation free energy of 17.3 ± 0.4 kcal/mol. The corresponding value for MAO B is 15.7 ± 0.7 kcal/mol. Both values are in good agreement with the estimated experimental barriers of 16.6 and 16.0 kcal/mol for MAO A and MAO B, respectively. The fact that we reproduced the kinetic data and preferential catalytic effect of MAO B over MAO A gives additional support to the validity of the proposed hydride transfer mechanism. Furthermore, we demonstrate that adrenaline is preferably involved in the reaction in a neutral rather than in a protonated form due to considerably higher barriers computed for the protonated adrenaline substrate. The results are discussed in the context of chemical mechanism of MAO enzymes and possible applications of multiscale simulation to rationalize the effects of MAO activity on adrenaline level.