13 reasons why the brain is susceptible to oxidative stress

Redox Biology, Journal Year: 2018, Volume and Issue: 15, P. 490 - 503

Published: Feb. 3, 2018

The human brain consumes 20% of the total basal oxygen (O2) budget to support ATP intensive neuronal activity. Without sufficient O2 demands, activity fails, such that, even transient ischemia is neurodegenerative. While essentiality function clear, how oxidative stress causes neurodegeneration ambiguous. Ambiguity exists because many reasons why susceptible remain obscure. Many are erroneously understood as deleterious result adventitious derived free radical and non-radical species generation. To understand underpin stress, one must first re-cast in a positive light their deliberate generation enables achieve critical functions (e.g. synaptic plasticity) through redox signalling (i.e. functionality). Using radicals derivatives signal sensitises when goes awry negative advance mechanistic understanding, we rationalise 13 stress. Key include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, active transition metals neurotransmitter auto-oxidation. We review RNA oxidation an underappreciated cause complex interplay between each reason dictates susceptibility dynamic context neural identity dependent manner. Our discourse sets stage for investigators interrogate biochemical basis health disease.

Language: Английский

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Semaphorin3A induces nerve regeneration in the adult cornea-a switch from its repulsive role in development

PLoS ONE, Journal Year: 2018, Volume and Issue: 13(1), P. e0191962 - e0191962

Published: Jan. 25, 2018

The peripheral sensory nerves that innervate the cornea can be easily damaged by trauma, surgery, infection or diabetes. Several growth factors and axon guidance molecules, such as Semaphorin3A (Sema3A) are upregulated upon injury. Nerves regenerate after injury but do not recover their original density patterning. Sema3A is a well known cone repellent protein during development, however its role in adult nerve regeneration remains undetermined. Here we investigated neuro-regenerative potential of on nervous system neurons those cornea. First, examined gene expression profile Semaphorin class 3 family members found all expressed However, there fast increase expression. We then corroborated totally abolished promoting effect factor (NGF) embryonic observed signs collapse axonal retraction 30 min addition. isolated trigeminal ganglia dorsal root neurons, did inhibited NGF-induced neuronal growth. Furthermore, treated with alone produced similar to cells NGF length neurites branching was comparable between both treatments. These effects were replicated vivo, where thy1-YFP neurofluorescent mice subjected epithelium debridement receiving intrastromal pellet implantation containing showed increased corneal than pellets vehicle. In PNS potent inducer vitro vivo. Our data indicates functional switch for well-described repulsive development changes adulthood. high normal injured corneas could related factor.

Language: Английский

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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

Pharmacological Reviews, Journal Year: 2021, Volume and Issue: 73(4), P. 1469 - 1658

Published: Oct. 1, 2021

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels critical to brain function and centrally implicated numerous psychiatric neurologic disorders. There different classes iGluRs with a variety receptor subtypes each class that play distinct roles neuronal functions. The diversity iGluR subtypes, their unique functional properties roles, has motivated large number studies. Our understanding advanced considerably since first subunit gene was cloned 1989, research focus expanded encompass facets biology have been recently discovered exploit experimental paradigms made possible technological advances. Here, we review insights from more than 3 decades studies an emphasis on progress occurred past decade. We cover structure, function, pharmacology, neurophysiology, therapeutic implications for all assembled subunits encoded 18 genes. SIGNIFICANCE STATEMENT: Glutamate important virtually aspects either involved mediating some clinical features neurological disease or represent target treatment. Therefore, pharmacology this will advance our many at molecular, cellular, system levels provide new opportunities treat patients.

Language: Английский

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Specification of synaptic connectivity by cell surface interactions

Nature reviews. Neuroscience, Journal Year: 2015, Volume and Issue: 17(1), P. 4 - 4

Published: Dec. 10, 2015

Language: Английский

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Semaphorins and plexins as therapeutic targets

Nature Reviews Drug Discovery, Journal Year: 2014, Volume and Issue: 13(8), P. 603 - 621

Published: Aug. 1, 2014

Language: Английский

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Branch management: mechanisms of axon branching in the developing vertebrate CNS

Nature reviews. Neuroscience, Journal Year: 2013, Volume and Issue: 15(1), P. 7 - 18

Published: Dec. 20, 2013

Language: Английский

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Understanding axon guidance: are we nearly there yet?

Development, Journal Year: 2018, Volume and Issue: 145(10)

Published: May 14, 2018

During nervous system development, neurons extend axons to reach their targets and form functional circuits. The faulty assembly or disintegration of such circuits results in disorders the system. Thus, understanding molecular mechanisms that guide lead neural circuit formation is interest not only developmental neuroscientists but also for a better comprehension disorders. Recent studies have demonstrated how crosstalk between different families guidance receptors can regulate axonal navigation at choice points, changes growth cone behaviour intermediate require surface expression receptors. These be achieved by variety mechanisms, including transcription, translation, protein-protein interactions, specific trafficking proteins mRNAs. Here, I review these axon highlighting most recent advances field challenge textbook model guidance.

Language: Английский

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The Versatile Tanycyte: A Hypothalamic Integrator of Reproduction and Energy Metabolism

Endocrine Reviews, Journal Year: 2018, Volume and Issue: 39(3), P. 333 - 368

Published: Jan. 17, 2018

The fertility and survival of an individual rely on the ability periphery to promptly, effectively, reproducibly communicate with brain neural networks that control reproduction, food intake, energy homeostasis. Tanycytes, a specialized glial cell type lining wall third ventricle in median eminence hypothalamus, appear act as linchpin these processes by dynamically controlling secretion neuropeptides into portal vasculature hypothalamic neurons regulating blood-brain blood–cerebrospinal fluid exchanges, both depend cells adapt their morphology physiological state individual. In addition barrier properties, tanycytes possess sense blood glucose levels, play fundamental active role shuttling circulating metabolic signals intake. Moreover, accumulating data suggest that, keeping putative descent from radial cells, are endowed stem properties may respond dietary or reproductive cues modulating neurogenesis. Tanycytes could thus constitute missing link loop connecting behavior, hormonal changes, signal transduction, central neuronal activation and, finally, behavior again. this article, we will examine recent advances understanding tanycytic plasticity function hypothalamus underlying molecular mechanisms. We also discuss involvement therapeutic potential disorders.

Language: Английский

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Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(3), P. 337 - 350

Published: Feb. 28, 2020

Language: Английский

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Axon guidance proteins in neurological disorders

The Lancet Neurology, Journal Year: 2015, Volume and Issue: 14(5), P. 532 - 546

Published: March 11, 2015

Language: Английский

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