The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.

/pdf/glutamate-receptor-ion-channels-structure-regulation-and-148yts0p6h.pdf

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease.

http://utsc.utoronto.ca/%7Ebritto/publications/amtox.pdf

NH4+ toxicity in higher plants: a critical review

This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration. Emphasis is placed on the physiology and pathophysiology of ATP, but extracellular roles of its breakdown product, adenosine, are also considered because of their intimate interactions. The early history of the involvement of ATP in autonomic and skeletal neuromuscular transmission and in activities in the central nervous system and ganglia is reviewed. Brief background information is given about the identification of receptor subtypes for purines and pyrimidines and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is a cotransmitter in most, if not all, peripheral and central neurons is presented, as well as full accounts of neurotransmission and neuromodulation in autonomic and sensory ganglia and in the brain and spinal cord. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to nonmuscular cells. To establish the primitive and widespread nature of purinergic neurotransmission, both the ontogeny and phylogeny of purinergic signaling are considered. Finally, the pathophysiology of purinergic neurotransmission in both peripheral and central nervous systems is reviewed, and speculations are made about future developments.

/pdf/physiology-and-pathophysiology-of-purinergic-1z94g2hz0f.pdf

Physiology and Pathophysiology of Purinergic Neurotransmission

510 hyperammonemia increases gabaergic tone in cerebellum but decreases it in cortex of rats. role in cognitive impairment

Ammonia toxicity was first reported by Pavlov and coworkers a century ago (1). They excluded the liver from the circulation and found that when dogs treated in this way were fed meat, they developed hyperammonemia, which was associated with coma and led to the death of the animal.

Control of urea synthesis and ammonia detoxification.

We developed a simple analytical method for the simultaneous determination of representatives of various groups of neurotoxic insecticides (carbaryl, chlorpyrifos, cypermethrin, and α-endosulfan and β-endosulfan and their metabolite endosulfan sulfate) in limited amounts of animal tissues containing different amounts of lipids. Selected tissues (rodent fat, liver, and brain) were extracted in a special in-house-designed mini-extractor constructed on the basis of the Soxhlet and Twisselmann extractors. A dried tissue sample placed in a small cartridge was extracted, while the nascent extract was simultaneously filtered through a layer of sodium sulfate. The extraction was followed by combined clean-up, including gel permeation chromatography (in case of high lipid content), ultrasonication, and solid-phase extraction chromatography using C18 on silica and aluminum oxide. Gas chromatography coupled with high-resolution mass spectrometry was used for analyte separation, detection, and quantification. Average recoveries for individual insecticides ranged from 82 to 111%. Expanded measurement uncertainties were generally lower than 35%. The developed method was successfully applied to rat tissue samples obtained from an animal model dealing with insecticide exposure during brain development. This method may also be applied to the analytical treatment of small amounts of various types of animal and human tissue samples. A significant advantage achieved using this method is high sample throughput due to the simultaneous treatment of many samples.

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor

A Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data

During brain development there is a strict control of the proliferation, migration and differentiation of neural stem cells to different cell types. Alterations in the control of these processes may result in altered balance in the formation of different cell types resulting in a long-lasting impairment of cerebral processes. This occurs for example if brain is exposed to alcohol during key stages of development which results in accelerated glial cells formation, impaired neuron formation and impaired cognitive function.

The molecular mechanisms modulating differentiation of neural stem cells to neurons or non neuronal cells are not well known. Nitric oxide (NO) plays a relevant role in this process. NO increases the activity of soluble guanylate cyclase and is a main modulator of cGMP levels in brain. It has been proposed that cGMP-mediated NO signalling may be involved in the early differentiation events of embryonic stem cells. If this is the case, pathological situations in which the production of cGMP is altered during brain development could lead to altered differentiation of stem cells to neurons or glial cells, resulting in cognitive impairment in the children. Moreover, normalizing cGMP levels in these situations could prevent the alterations in neural stem cells differentiation and cognitive impairment.

https://link.springer.com/content/pdf/10.1186%2F1471-2210-11-S1-O29.pdf

Vicente Felipo

Papers

510 hyperammonemia increases gabaergic tone in cerebellum but decreases it in cortex of rats. role in cognitive impairment

Control of urea synthesis and ammonia detoxification.

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor

A Nextflow pipeline for T-cell receptor repertoire reconstruction and analysis from RNA sequencing data

cGMP modulates stem cells differentiation to neurons in brain in vivo pathological implications