Protective effects of intranasal oxytocin on cognitive dysfunction and hippocampal synaptic plasticity impairment induced by scopolamine

Abstract

Alzheimer's disease (AD) is a progressive neurological disorder that leads to cognitive dysfunction and synaptic plasticity impairment. Recently, the role of neuropeptide oxytocin (OT) in ameliorating neurodegenerative diseases with cognitive disorders has attracted attention. The present study was designed to examine the protective effect of chronic treatment with intranasal OT on anxiety, memory, synaptic plasticity, and hippocampal cell degeneration in an adult rat model of AD. AD was induced by administration of SCO (1 mg/kg) for 7 days intraperitoneally. 40 wistar rats (220–250 g) were randomly assigned to five groups (n = 8 rats/group)—group I: control, group II: SCO, group III: OT (2 μg/kg, 7 days, IN), group IV: OT+SCO and group V: DON+SCO (donepezil, 3 mg/kg, 7 days, ip). Anxiety-like behavior and memory performance were assessed using the elevated plus maze and passive avoidance tests, respectively. Additionally, synaptic plasticity was measured by evaluating the population spike (PS) amplitude and the slope of excitatory postsynaptic potentials (fEPSP) in the dentate gyrus (DG) region. Histological analysis of the hippocampus, focusing on the CA1 and CA3 regions, was conducted using hematoxylin and eosin staining. Furthermore, oxidative stress markers, including malondialdehyde (MDA) and total antioxidant capacity (TAC) (measured via the FRAP assay), were assessed in both plasma and hippocampal tissue. The results indicated that SCO injection resulted in deficits in passive avoidance memory, heightened anxiety-like behavior, impaired LTP induction in DG (decrease PS amplitude and fEPSP slope), and increased degeneration of hippocampal cells. In addition, SCO injection significantly elevated malondialdehyde (MDA) levels and reduced in the SCO group. Oxytocin treatment notably improved LTP impairment, reflected by enhanced PS amplitude and fEPSP slope in the hippocampus of SCO-treated rats, which was correlated with improvements in memory deficits and reduced anxiety. These effects were supported by the mitigation of histological damage in the CA1 and CA3 hippocampal regions. Moreover, OT significantly corrected the SCO-induced increase in MDA and decrease in TAC. The beneficial effects of OT were comparable to those of the standard drug, donepezil. In conclusion, chronic intranasal administration of OT may prevent SCO-induced anxiety and memory impairments by enhancing neuronal plasticity, potentially due to its antioxidant properties.