Intranasal Oxytocin Attenuates Cognitive Impairment, β-Amyloid Burden and Tau Deposition in Female Rats with Alzheimer's Disease: Interplay of ERK1/2/GSK3β/Caspase-3

Oxytocin is a neuropeptide hormone that plays an important role in social bonding and behavior. Recent studies indicate that oxytocin could be involved in the regulation of neurological disorders. However, its role in modulating cognition in Alzheimer's disease (AD) has never been explored. Hence, the present study aims to investigate the potential of chronic intranasal oxytocin in halting memory impairment & AD pathology in aluminum chloride-induced AD in female rats. Morris water maze was used to assess cognitive dysfunction in two-time points throughout the treatment period. In addition, neuroprotective effects of oxytocin were examined by assessing hippocampal acetylcholinesterase activity, beta-amyloid 1-42 protein, and Tau levels. In addition, ERK1/2, GSK3 beta, and caspase-3 levels were assessed as chief neurobiochemical mediators in AD. Hippocampi histopathological changes were also evaluated. These findings were compared to the standard drug galantamine alone and combined with oxytocin. Results showed that oxytocin restored cognitive functions and improved animals' behavior in the Morris test. This was accompanied by a significant decline in acetylcholinesterase activity, 1-42 beta-amyloid and Tau proteins levels. Hippocampal ERK1/2 and GSK3 beta were also reduced, exceeding galantamine effects, thus attenuating AD pathological hallmarks formation. Determination of caspase-3 revealed low cytoplasmic positivity, indicating the ceasing of neuronal death. Histopathological examination confirmed these findings, showing restored hippocampal cells structure. Combined galantamine and oxytocin treatment showed even better biochemical and histopathological profiles. It can be thus concluded that oxytocin possesses promising neuroprotective potential in AD mediated via restoring cognition and suppressing beta-amyloid, Tau accumulation, and neuronal death.

Automated summary

Oxytocin has neuroprotective potential in Alzheimer's disease, restoring cognition and suppressing beta-amyloid, Tau accumulation, and neuronal death. Combined treatment with galantamine and oxytocin shows better biochemical and histopathological profiles.