Cholinesterase inhibitors ameliorate spatial learning deficits in rats following hypobaric hypoxia.

Abstract

Cognitive functions especially learning and memory are severely affected by high altitude (HA) exposure. Hypobaric hypoxia (HBH) encountered at HA is known to cause oxidative stress, alterations of neurotransmitters and cognitive impairment. We hypothesized that alteration in cholinergic system may be involved in HBH-induced learning impairment. The present study has investigated the cholinergic dysfunctions associated with simulated HBH-induced impairment of learning in rats and protective role of acetylcholine esterase inhibitors (AChEIs). Male Sprague-Dawley rats were exposed to HBH equivalent to 6,100 m for 7 days in a simulated decompression chamber. After stipulated period of exposure, learning ability was assessed using Morris water maze (MWM) task. Cholinergic markers like acetylcholine (ACh) and acetyl cholinesterase (AChE) were evaluated from cortex and hippocampus. Morphological changes were evaluated from cortex, CA1, and CA3 region of hippocampus by Nissle staining and by electron microscopy. We found that exposure to HBH led to impairment of learning ability in MWM task, and it was accompanied by decrease in ACh level, increase in AChE activity, and revealed critical cellular damage. Administration of AChEIs like physostigmine (PHY) and galantamine (GAL) resulted in amelioration of the deleterious effects induced by HBH. The AChEIs were also able to restore the neuronal morphology. Our data suggest that cholinergic system is affected by HBH, and AChEIs were able to improve HBH-induced learning impairment in rats.