Alpha7 Nicotinic Acetylcholine Receptor Down Regulation Impairs Mitochondrial Function in Streptozotocin-induced Sporadic Alzheimer's Disease Model in Rats

Background/Aim: Alzheimer's disease (AD), a type of neurodegenerative disorder, possesses significant memory loss as one of the cardinal manifestations. The pathophysiology of AD includes increased accumulation of A beta, degeneration of cholinergic activity and mitochondrial dysfunction. Nicotinic acetylcholine receptors (nAChRs) especially alpha7 nicotinic acetylcholine receptors (alpha 7 nAChRs) are widely distributed in brain and associated with memory function. Further, we explored the correlation between the mitochondrial dysfunction and the expression level of alpha 7 nAChRs in STZ challenged brain regions of rats. Materials and Methods: The STZ group rats received intracerebroventricular infusion of STZ (3 mg/kg) on D-1 and D-3 of experimental design of 18 days. Behavioral parameters ware investigated using MWM and Y-maze test paradigm. Further, biochemical analysis was assessed in all three regions of rats. Results: STZ administration caused significant impairment in memory and learning of rats MWM and Y-maze test paradigm. There was significant decrease in level expression of alpha 7 nAChRs and cholinergic functions in terms of elevated AChE activity and decreased ACh level and ChAT activity in rat hippocampus, pre-frontal cortex and amygdala. Further, STZ administration significantly attenuated the mitochondrial function, integrity and bioenergetics in all the selected brain regions. Interestingly, the intracerebroventricular infusion of STZ increased A beta level in all the rat brain regions. Conclusion: The alpha 7 nAChR down regulation may form a basis to cognitive deficits along with cholinergic dysfunction, A beta accumulation and mitochondrial dysfunction in memory sensitive rat brain regions. Thus, alpha 7 nAChR could be an alternative and potential target in the management of AD.

Automated summary

The study investigated the correlation between mitochondrial dysfunction and the expression level of alpha 7 nAChRs in STZ challenged brain regions of rats. Results showed that STZ caused significant impairment in memory and learning, with decreased expression of alpha 7 nAChRs and cholinergic functions in rat hippocampus, pre-frontal cortex and amygdala. STZ administration also attenuated mitochondrial function and increased A beta level in all selected brain regions.