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

IF 1.7 4区心理学 Q3 PSYCHOLOGY, BIOLOGICAL

Learning and Motivation Pub Date : 2025-02-01 DOI:10.1016/j.lmot.2025.102094

F. Houshmand , Khalili Gh , S. Shabani , M. Anjomshoa , M. Shahrani , S. Najafi-Chaleshtori , F. Azizi

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引用次数: 0

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.

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鼻内催产素对东莨菪碱诱导的认知功能障碍和海马突触可塑性损伤的保护作用

阿尔茨海默病（AD）是一种进行性神经系统疾病，可导致认知功能障碍和突触可塑性损伤。近年来，神经肽催产素（OT）在改善神经退行性疾病伴认知障碍中的作用引起了人们的关注。本研究旨在探讨鼻内OT慢性治疗对成年AD大鼠模型的焦虑、记忆、突触可塑性和海马细胞变性的保护作用。采用SCO（1 mg/kg）腹腔注射7 d诱导AD。40只wistar大鼠（220 ~ 250 g）随机分为5组（n = 8只/组）：ⅰ组：对照组、ⅱ组：SCO、ⅲ组：OT（2 μg/kg, 7 d， IN）、ⅳ组：OT+SCO和ⅴ组：DON+SCO（多奈哌齐，3 mg/kg, 7 d, ip）。焦虑样行为和记忆表现分别采用升高加迷宫和被动回避测试进行评估。此外，通过评估齿状回（DG）区的群体峰（PS）振幅和兴奋性突触后电位（fEPSP）斜率来测量突触可塑性。采用苏木精和伊红染色对海马进行组织学分析，重点观察CA1和CA3区域。此外，在血浆和海马组织中评估氧化应激标志物，包括丙二醛（MDA）和总抗氧化能力（TAC）（通过FRAP测定）。结果表明，SCO注射导致大鼠被动回避记忆缺失，焦虑样行为增强，DG LTP诱导功能受损（PS振幅和fEPSP斜率降低），海马细胞变性增加。此外，SCO注射显著升高丙二醛（MDA）水平，SCO组降低。催产素处理显著改善了LTP损伤，表现为sco处理大鼠海马PS振幅和fEPSP斜率增强，这与记忆缺陷改善和焦虑减轻有关。这些作用得到了海马CA1和CA3区组织学损伤减轻的支持。此外，OT显著纠正了sco诱导的MDA升高和TAC降低。OT的有益效果与标准药物多奈哌齐相当。总之，慢性鼻内给药OT可能通过增强神经元可塑性来预防sco诱导的焦虑和记忆障碍，这可能是由于其抗氧化特性。

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来源期刊

Learning and Motivation Multiple-

CiteScore

2.90

自引率

0.00%

发文量

期刊介绍： Learning and Motivation features original experimental research devoted to the analysis of basic phenomena and mechanisms of learning, memory, and motivation. These studies, involving either animal or human subjects, examine behavioral, biological, and evolutionary influences on the learning and motivation processes, and often report on an integrated series of experiments that advance knowledge in this field. Theoretical papers and shorter reports are also considered.