Department of Anatomical Sciences, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Neuroscience. 2022 Aug 1;496:64-72. doi: 10.1016/j.neuroscience.2022.06.012. Epub 2022 Jun 11.
To determine detrimental effects of estrogen and insulin deficiencies on hippocampus, we examined apoptosis-induced neuronal damage and cholinergic system in ovariectomized and/or diabetic rat hippocampus. Possible neuroprotective effects of treadmill exercise were also investigated. Adult female Wistar rats were randomly divided into four groups (n = 5 rats/group) as follows: control, ovariectomized (Ovx), diabetic (Dia, streptozotocin (STZ) 60 mg/kg; i.p.), and Ovx + Dia groups. Each group was further subdivided into exercise and non-exercise groups. Animals in exercise groups were subjected to treadmill training, while those in non-exercise groups were placed on the stationary treadmill for 4 weeks (5 days/week). Apoptosis-related protein levels (i.e. Bax, Bcl-2, and caspase-3), number of survived neurons, and acetylcholinesterase (AChE) activity in the hippocampus were measured using Western blotting, Cresyl Violet staining, and Ellman assay, respectively. Both ovariectomy and diabetes increased expression of Bax and caspase-3 and decreased expression of Bcl-2 at protein levels. In addition, a significant decrease in the number of survived neurons was observed in both Ovx and Dia groups, while AChE activity was lower only in the Dia group. The Ovx + Dia group showed stronger apoptosis-induced neuropathology and inhibition of AChE activity. Treadmill exercise attenuated apoptosis-induced neuropathology in the Ovx and Dia groups and recovered AChE activity in the Dia group. Neuroprotective effects of treadmill exercise were mediated by inhibition of apoptosis. Moderate exercise protocol had no beneficial anti-apoptotic and neuroprotective effects in ovariectomized-diabetic rats.
为了确定雌激素和胰岛素缺乏对海马体的有害影响，我们检查了卵巢切除和/或糖尿病大鼠海马体中的凋亡诱导神经元损伤和胆碱能系统。还研究了跑步机运动的可能神经保护作用。成年雌性 Wistar 大鼠被随机分为四组（每组 5 只大鼠）：对照组、卵巢切除组（Ovx）、糖尿病组（糖尿病，链脲佐菌素（STZ）60mg/kg；腹腔注射）和 Ovx+Dia 组。每组进一步分为运动和非运动组。运动组的动物接受跑步机训练，而非运动组的动物则在固定的跑步机上放置 4 周（每周 5 天）。使用 Western blot 法测量海马体中与凋亡相关的蛋白水平（即 Bax、Bcl-2 和 caspase-3）、存活神经元的数量以及乙酰胆碱酯酶（AChE）活性。卵巢切除术和糖尿病均增加了 Bax 和 caspase-3 的蛋白表达，并降低了 Bcl-2 的表达。此外，在 Ovx 和 Dia 组中均观察到存活神经元数量的显着减少，而仅在 Dia 组中 AChE 活性降低。Ovx+Dia 组显示出更强的凋亡诱导神经病理学和 AChE 活性抑制。跑步机运动减轻了 Ovx 和 Dia 组中的凋亡诱导神经病理学，并恢复了 Dia 组中的 AChE 活性。跑步机运动的神经保护作用是通过抑制细胞凋亡介导的。适度的运动方案对卵巢切除和糖尿病大鼠没有有益的抗凋亡和神经保护作用。
