Aims: Evidence suggests that hypobaric hypoxia (HH) exposure causes biochemical and molecular level perturbations in brain resulting in associated cognitive dysfunction. However, the possible effect of HH on amygdala and the associated limbic regions based functions remains elusive. Regulated fear expression is essential for quick adaptations and optimal behavioral response. Therefore, the present study aims to investigate the effect of HH on biochemical and molecular mechanisms in amygdala involved in fear memory regulation along with the hippocampus and prefrontal cortex based fear memory.
Materials and methods: Adult male Sprague Dawley rats were subjected to cued and contextual fear memory assessment following simulated HH exposure (25,000 ft) for 3 and 7 days. Plasma and limbic tissue (Prefrontal cortex, hippocampus and amygdala) samples were collected for biochemical and molecular studies.
Key findings: Results revealed a decrease in contextual and cued fear memory retrieval, indicating fear memory dysregulation under HH exposure. Increased level of norepinephrine, dopamine, corticosterone and glutamate along with a decline in serotonin and GABA level was observed in plasma and limbic tissue after 3 and 7 days of HH exposure. Dysregulation of neuromodulation, neuronal survival and synaptic homeostasis was also evident from observed decline in tryptophan hydroxylase, BDNF, synaptophysin, synapsin1, PSD95 and an increase in tyrosine hydroxylase immunoreactivity in limbic region under HH exposure.
Significance: Dysregulation of limbic region signaling molecules associated with survival and maintenance of synaptic plasticity (Synaptophysin, synapsin1 and PSD95), neurotrophic factor (BDNF) and shift in monoamines, corticosterone, glutamate and GABA levels may contribute to the HH induced fear memory impairment.
Keywords: Corticosterone; Fear memory; GABA; Glutamate; Hypobaric hypoxia; Monoamines; Synaptic plasticity.
Copyright © 2020. Published by Elsevier Inc.