Basir Hamid Shokati, Mirazi Naser, Komaki Alireza, Mohamadpour Behnam, Hosseini Abdolkarim
Department of Biology, Faculty of Basic Science, Bu-Ali Sina University, Hamedan, Iran.
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Mol Neurobiol. 2025 Feb;62(2):2548-2560. doi: 10.1007/s12035-024-04388-x. Epub 2024 Aug 13.
Alzheimer's disease (AD) is a progressive neurological disorder characterized by cognitive decline. This study was undertaken to evaluate the effects of selegiline (SEL) against AD-induced cognitive deficits and explore the possible involved mechanisms. AD was induced by unilateral intracerebroventricular (U-ICV) injection of 5 μg of amyloid beta (Aβ), and oral administration of SEL (0.5 mg/kg/day) was performed for 30 consecutive days. Aβ injection resulted in spatial cognitive decline, as demonstrated by a decrease in the time spent in the target zone on the probe day (P < 0.01) in the Barnes maze test (BMT). This spatial cognitive decline was associated with disrupted synaptic plasticity, as indicated by reductions in both components of hippocampal long-term potentiation (LTP), namely population spike amplitude (P < 0.001) and field excitatory postsynaptic potential (P < 0.001). On the other hand, the injection of Aβ resulted in oxidative stress by decreasing total thiol group (TTG) content and increasing malondialdehyde (MDA) levels in the rat plasma (P < 0.001). Additionally, the number of healthy cells in the hippocampal dentate gyrus (DG) and CA1 regions was reduced in AD rats (P < 0.001). However, oral administration of SEL improved spatial cognitive decline in the Aβ-induced AD rats. The results suggest that improvement of neuroplasticity deficiency, regulation of oxidant/antioxidant status, and suppression of neuronal loss by SEL may be the mechanisms underlying its beneficial effect against AD-related spatial cognitive impairment.
阿尔茨海默病（AD）是一种以认知功能衰退为特征的进行性神经疾病。本研究旨在评估司来吉兰（SEL）对AD所致认知缺陷的影响，并探究其可能涉及的机制。通过单侧脑室内（U-ICV）注射5μg淀粉样β蛋白（Aβ）诱导AD模型，连续30天口服给予SEL（0.5mg/kg/天）。在巴恩斯迷宫试验（BMT）中，Aβ注射导致空间认知衰退，表现为在探测日目标区域停留时间减少（P<0.01）。这种空间认知衰退与突触可塑性破坏有关，海马长时程增强（LTP）的两个组成部分均降低，即群体峰电位幅度（P<0.001）和场兴奋性突触后电位（P<0.001）。另一方面，Aβ注射通过降低大鼠血浆中总巯基（TTG）含量和增加丙二醛（MDA）水平导致氧化应激（P<0.001）。此外，AD大鼠海马齿状回（DG）和CA1区的健康细胞数量减少（P<0.001）。然而，口服SEL可改善Aβ诱导的AD大鼠的空间认知衰退。结果表明，SEL改善神经可塑性缺陷、调节氧化/抗氧化状态以及抑制神经元丢失可能是其对AD相关空间认知障碍产生有益作用的潜在机制。
