Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats

Abstract

Microgravity induces a redistribution of blood volume. Consequently, astronauts' body pressure is modified so that the upright blood pressure gradient is abolished, thereby inducing a modification in cerebral blood pressure. This effect is mimicked in the hindlimb unloaded rat model. After a duration of 8 days of unloading, Ca 2+ signals activated by depolarization and inositol-1,4,5-trisphosphate intracellular release were increased in cerebral arteries. In the presence of ryanodine and thapsigargin, the depolarization-induced Ca 2+ signals remained increased in hindlimb suspended animals, indicating that Ca 2+ influx and Ca 2+ -induced Ca 2+ release mechanism were both increased. Spontaneous Ca 2+ waves and localized Ca 2+ events were also investigated. Increases in both amplitude and frequency of spontaneous Ca 2+ waves were measured in hindlimb suspension conditions. After pharmacological segregation of Ca 2+ sparks and Ca 2+ sparklets, their kinetic parameters were characterized. Hindlimb suspension induced an increase in the frequencies of both Ca 2+ localized events, suggesting an increase of excitability. Labeling with bodipy compounds suggested that voltage-dependent Ca 2+ channels and ryanodine receptor expressions were increased. Finally, the expression of the ryanodine receptor subtype 1 (RyR1) was increased in hindlimb unloading conditions. Taken together, these results suggest that RyR1 expression and voltage-dependent Ca 2+ channels activity are the focal points of the regulation of Ca 2+ signals activated by vasoconstriction in rat cerebral arteries with an increase of the voltage-dependent Ca 2+ influx.

Simulated Microgravity Subtlety Changes Monoamine Function across the Rat Brain

“…We confirmed the slight physiological modifications previously observed under SMG in laboratory animals: (1) the stop of the natural increase body weight even for a small period of 7 days, also observed during spaceflight [34][35][36][37][38], (2) the decrease of water intake only during the first 1-3 days of suspension [35,39,40], and (3) the absence of alteration of glycemia [41], food intake [34], and body temperature [34]. The impact of SMG on plasma corticosterone level is under debate and probably reveals hypersensitivity to stressors related to suspension.…”

Deep Membrane Proteome Profiling of Rat Hippocampus in Simulated Complex Space Environment by SWATH

“…During space travelling, astronauts may come across extreme environmental conditions such as microgravity, noise, radiation, confinement, and circadian rhythm disorder [1][2][3]. Previous studies focused mainly on physiological and psychological changes such as bone mineral loss [4][5][6], cardiovascular disruption [7][8][9], immune system malfunctioning [10][11][12], cognitive dysfunction [13][14][15][16], risky decision making, bad mood status, and high depression levels [1,17,18] under the microgravity [19][20][21]. Few reports explore how the extreme complex space environment affects astronauts' physiological and psychological functions.…”

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

“…Since gravity changes induce modifications of genome expression in several tissues (Morel et al, 2014), we hypothesized that hypergravity as well as stress (induced by acute or chronic administration of corticosterone) could affect the genome expression in the hippocampus, with putative effects on memory. In fact, modifications of spatial memory have been previously suggested in rat exposed to hypergravity (Mitani et al, 2004).…”