Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment...

Area of Science:

• Neuroscience
• Cellular and Molecular Biology

Background:

• Cholinergic dysfunction contributes to learning and memory deficits during hypoxia.
• Inflammatory mediators, such as inducible nitric oxide synthase (iNOS), are known to impair cholinergic neuron function.

Purpose of the Study:

• To investigate the role of iNOS-mediated signaling in retrograde and anterograde memory impairment following acute hypobaric hypoxia.
• To explore the effects of hypoxia on cholinergic function and oxidative stress markers in the cerebral cortex and hippocampus.

Main Methods:

• Acute hypobaric hypoxia was induced in Balb/c mice (23,000 ft for 6h).
• Memory function was assessed using elevated plus maze and passive avoidance step-through tasks.
• iNOS expression, nitric oxide (NO) levels, acetylcholinesterase (AChE) activity, and lipid peroxidation were measured post-hypoxia.
• Mice were treated with aminoguanidine (an iNOS inhibitor) or a NO donor (spermine NONOate).

Main Results:

• Hypoxia caused transient retrograde memory impairment, with no effect on anterograde memory.
• A significant increase in iNOS expression and NO levels was observed in the cerebral cortex on days 2 and 3 post-hypoxia.
• Aminoguanidine treatment reversed hypoxia-induced retrograde memory impairment and reduced iNOS/NO levels.
• Reduced AChE activity and increased lipid peroxidation were noted in the cerebral cortex post-hypoxia, but not in the hippocampus.
• In vitro, a NO donor inhibited AChE activity in a concentration-dependent manner.

Conclusions:

• Nitric oxide (NO) surge, resulting from iNOS upregulation during hypoxia, disrupts memory consolidation by altering cholinergic functions.
• The cerebral cortex is particularly affected by hypoxia-induced cholinergic dysfunction and oxidative stress.
• Targeting iNOS may be a therapeutic strategy for mitigating hypoxia-related memory deficits.