LAUSR

AIMS Evidences suggest that hypobaric hypoxia (HH) exposure causes biochemical and molecular level perturbations in brain resulting to associated cognitive dysfunction. However, possible effect of HH on amygdala and the associated limbic regions (prefrontal cortex and hippocampus) 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 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) were collected for biochemical and molecular studies. KEY FINDINGS Results revealed a decrement in contextual and cued fear memory retrieval, indicating to 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, 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 increase in tyrosine hydroxylase immunoreactivity in limbic region under HH exposure. SIGNIFICANCE Dysregulation of limbic region's 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 basal levels may contribute to the HH induced fear memory impairment.