High Pressure Stress Response: Involvement of NMDA Receptor Subtypes and Molecular Markers

Abstract

Professional divers who are exposed to high pressure (HP) above 1.1 MPa suffer from high pressure neurological syndrome (HPNS), which is characterized by reversible CNS hyperexcitability and cognitive and motor deficits. HPNS remains the final major constraints on deep diving at HP. Prolonged and repetitive exposure to HP during deep sea saturation dives may result in permanent memory and motor impairment. Previous studies revealed that CNS hyperexcitability associated with HPNS is largely induced by N-methyl-D-aspartate receptors (NMDARs). NMDARs that contain the GluN2A subunit are the only ones that show a large (∼60%) current increase at He HP. NMDAR subtypes that contain other GluN2 members show minor decrease or no change of the current. Immunoprecipitation was used in order to test the hypothesis that current augmentation may result from inserting additional NMDARs into the membrane during the 20–25 min compression. The results indicated that there is no increase in surface expression of NMDARs in the oocyte membrane under HP conditions. In contrast, consistent increase in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin was discovered. GAPDH and β-actin are cytosolic proteins which involve in various cellular control processes, increase of their expression suggests the presence of a general cellular stress response to HP. Understanding the precise hyperexcitation mechanism(s) of specific NMDAR subtypes and other possible neurotoxic processes during HP exposure could provide the key for eliminating the adverse, yet reversible, short-term effects of HPNS and hopefully the deleterious long-term ones.

The Mechanism of NMDA Receptor Hyperexcitation in High Pressure Helium and Hyperbaric Oxygen

“…The present study and our previous investigations (Bliznyuk et al, 2015(Bliznyuk et al, , 2016(Bliznyuk et al, , 2019b have demonstrated that aggregate formation, modified stoichiometry, alterations in glutamate and glycine affinity, and an increase in the number of receptors exposed on the membrane, cannot explain the increase in current (input-conductance) of NMDAR containing the GluN2A subunit. Yet our molecular dynamics simulations (Bliznyuk et al, 2019a) have indeed suggested that hydrostatic pressure and compression with He may cause alterations in NMDAR protein conformation.…”

Quercetin alleviates chronic unpredictable mild stress‐induced depression‐like behavior by inhibiting NMDAR1 with α2δ‐1 in rats

“…NMDAR is considered a classical ionotropic channel that plays a central role in neuronal communication 12 . It has been pointed out that the action of Glu on NMDAR leads to the recurrent opening of the Ca 2+ channel, which then causes an increase in the excitability of Glu neurons and PVN‐CRH neurons and leads to the hyperfunction of HPA axis, thus inducing depressive symptoms 49 . The results from Western blotting and immunofluorescence experiments showed that the expression level of NMDAR1 in the hypothalamus of CUMS rats was up‐regulated, which was then significantly down‐regulated after Que treatment.…”

Scutellarin ameliorates the stress‐induced anxiety‐like behaviors in mice by regulating neurotransmitters

“…We also investigated the roles of glutamate receptors during stress‐induced anxiety. Previous studies have shown that the GluN2 subunit of the NMDA receptor is involved in the response to stressful states (Bliznyuk, Hollmann, & Grossman, 2019). NMDA‐R regulates behavioral despair induced by amphetamine withdrawal, which indicates that NMDA‐R receptor plays an important role in the regulation of mood disorders (Haj‐Mirzaian et al, 2018).…”