Pressure Effects on Mammalian Central Nervous System

Grossman, Yoram; Aviner, Ben; Mor, Amir

doi:10.1201/9781439843611-c8

Cited by 11 publications

(12 citation statements)

References 1 publication

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“…The susceptibility to and symptom intensity of HPNS depend on the compression rate and absolute pressure. It is conceivable that this constellation of signs and symptoms arises from disturbances in the synaptic activity of neuronal networks (Grossman et al ., ). Additionally, the prolonged repetitive deep‐sea operation of professional divers at HP may result in permanent memory and motor impairment (Gronning & Aarli, ).…”

Section: Introductionmentioning

confidence: 97%

The N‐methyl‐D‐aspartate receptor's neglected subunit – GluN1 matters under normal and hyperbaric conditions

Bliznyuk

Aviner

Golan

et al. 2015

Eur J of Neuroscience

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Professional deep-water divers exposed to hyperbaric pressure (HP) above 1.1 MPa develop high-pressure neurological syndrome, which is associated with central nervous system hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible neuronal damage. In addition, we have reported that HP (10.1 MPa) differentially affects ionic currents, measured by the two-electrode voltage-clamp technique, of eight specific NMDAR subtypes generated by the co-expression of GluN1-1a or GluN1-1b with one of the four GluN2(A-D) subunits in Xenopus laevis oocytes. We now report that eight GluN1 splice variants, when co-expressed with GluN2A, mediate different ionic currents at normal and HP (5.1 MPa). These data, in conjunction with our previous results, indicate that both GluN1 and GluN2 subunits play a critical role in determining NMDAR currents under normal and HP conditions. These data, given the differential spatial distribution of the different NMDAR subtypes in the central nervous system, may offer a partial explanation for the mechanism governing the complex signs and symptoms of high-pressure neurological syndrome, and an explanation for the suspected long-term HP health decrement due to repetitive deep dives by professional divers.

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Section: Introductionmentioning

confidence: 97%

The N‐methyl‐D‐aspartate receptor's neglected subunit – GluN1 matters under normal and hyperbaric conditions

Bliznyuk

Aviner

Golan

et al. 2015

Eur J of Neuroscience

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“…HPNS susceptibility and symptoms intensity depend on the compression rate and on the absolute ambient pressure. It is conceivable that this constellation of signs and symptoms origins in disturbances in synaptic activity of neuronal networks (Grossman et al, 2010 ). In addition to HPNS, prolonged repetitive deep sea operations of professional divers at HP may result in permanent memory and motor impairment (Gronning and Aarli, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

The Enigma of the Dichotomic Pressure Response of GluN1-4a/b Splice Variants of NMDA Receptor: Experimental and Statistical Analyses

Bliznyuk

Gradwohl

Hollmann

et al. 2016

Front. Mol. Neurosci.

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Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with central nervous system (CNS) hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. Our laboratory has reported differential current responses under HP conditions in NMDAR subtypes that contain either GluN1-1a or GluN1-1b splice variants co-expressed in Xenopus laevis oocytes with all four GluN2 subunits. Recently, we reported that the increase in ionic currents measured under HP conditions is also dependent on which of the eight splice variants of GluN1 is co-expressed with the GluN2 subunit. We now report that the NMDAR subtype that contains GluN1-4a/b splice variants exhibited “dichotomic” (either increased or decreased) responses at HP. The distribution of the results is not normal thus analysis of variance (ANOVA) test and clustering analysis were employed for statistical verification of the grouping. Furthermore, the calculated constants of alpha function distribution analysis for the two groups were similar, suggesting that the mechanism underlying the switch between an increase or a decrease of the current at HP is a single process, the nature of which is still unknown. This dichotomic response of the GluN1-4a/b splice variant may be used as a model for studying reduced response in NMDAR at HP. Successful reversal of other NMDAR subtypes response (i.e., current reduction) may allow the elimination of the reversible malfunctioning short term effects (HPNS), or even deleterious long term effects induced by increased NMDAR function during HP exposure.

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“…Animals and humans exposed to ambient pressure above 1.1 MPa (100 m depth) develop High Pressure Neurological Syndrome (HPNS; Bennett and Rostain, 2003; Grossman et al, 2010), which is characterized by reversible but significant cognitive and motor decrements. At greater depths, myoclonia, convulsions, and seizures occur, indicating CNS hyperexcitability.…”

Section: Introductionmentioning

confidence: 99%

Pressure-selective modulation of NMDA receptor subtypes may reflect 3D structural differences

Mor¹,

Kuttner²,

Levy³

et al. 2012

Front. Cell. Neurosci.

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Professional deep-water divers exposed to high pressure (HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome (HPNS), which is associated with CNS hyperexcitability. We have previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible neuronal damage. We now report that HP (10.1 MPa) differentially affects eight specific NMDAR subtypes. GluN1(1a or 1b) was co-expressed with one of the four GluN2(A–D) subunits in Xenopus laevis oocytes. HP increased ionic currents (measured by two electrode voltage clamps) of one subtype, reduced the current in four others, and did not affect the current in the remaining three. 3D theoretical modeling was aimed at revealing specific receptor domains involved with HP selectivity. In light of the information on the CNS spatial distribution of the different NMDAR subtypes, we conclude that the NMDAR's diverse responses to HP may lead to selective HP effects on different brain regions. These discoveries call for further and more specific investigation of deleterious HP effects and suggest the need for a re-evaluation of deep-diving safety guidelines.

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Pressure Effects on Mammalian Central Nervous System

Cited by 11 publications

References 1 publication

The N‐methyl‐D‐aspartate receptor's neglected subunit – GluN1 matters under normal and hyperbaric conditions

The N‐methyl‐D‐aspartate receptor's neglected subunit – GluN1 matters under normal and hyperbaric conditions

The Enigma of the Dichotomic Pressure Response of GluN1-4a/b Splice Variants of NMDA Receptor: Experimental and Statistical Analyses

Pressure-selective modulation of NMDA receptor subtypes may reflect 3D structural differences

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