Department of Neurology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
J Mol Neurosci. 2010 May;41(1):145-55. doi: 10.1007/s12031-009-9311-7. Epub 2009 Dec 2.
The purposes of this research were to study the restoration on the cognitive ability of rat models with vascular dementia (VaD) by repetitive transcranial magnetic stimulation (rTMS) treatment and its impacts on synaptic plasticity in hippocampal CA1 area and to further explore the molecular mechanisms of the rTMS treatment on vascular dementia. Thirty-six male Wistar rats were randomly divided into four groups: the normal control group, the vascular dementia model group, the low-frequency rTMS group, and the high-frequency rTMS group. Two-vessel occlusion was employed to make VaD models. Low-frequency rTMS group rats were treated with 0.5 Hz rTMS for 6 weeks. High-frequency rTMS group rats underwent 5 Hz rTMS for 6 weeks. Morris water maze was carried out to detect the ability of spatial learning and memory of rats. The ultra-structural changes of synapses in four groups were observed by transmission electron microscope. Then the expressions of brain-derived neurotrophic factor (BDNF), NMDAR1, and Synaptophysin (SYN) mRNA and proteins in hippocampal CA1 area were determined by real-time PCR, western blot, and immunohistochemistry assay. After rTMS treatment, the learning and memory abilities of VaD rats improved significantly. The ultra-structures of synapses in hippocampal CA1 area in rTMS groups were reformed. The mRNA and protein expressions of BDNF, NMDAR1, and SYN in the low-frequency rTMS group and in the high-frequency rTMS group were higher than that in VaD model group (P < 0.05). rTMS plays an important and beneficial role in the restoration treatment of vascular dementia, which may be related to the mechanism that rTMS can increase the mRNA and protein expressions of BDNF, NMDAR1, and SYN and affect the synaptic plasticity in hippocampal CA1 area.
本研究旨在探讨重复经颅磁刺激（rTMS）治疗对血管性痴呆（VaD）大鼠模型认知功能的恢复作用及其对海马 CA1 区突触可塑性的影响，并进一步探讨 rTMS 治疗血管性痴呆的分子机制。将 36 只雄性 Wistar 大鼠随机分为四组：正常对照组、血管性痴呆模型组、低频 rTMS 组和高频 rTMS 组。采用二血管阻断法制作 VaD 模型。低频 rTMS 组大鼠接受 0.5 Hz rTMS 治疗 6 周，高频 rTMS 组大鼠接受 5 Hz rTMS 治疗 6 周。采用 Morris 水迷宫检测大鼠的空间学习记忆能力。透射电镜观察四组大鼠突触的超微结构变化。采用实时 PCR、Western blot 和免疫组织化学法检测海马 CA1 区脑源性神经营养因子（BDNF）、NMDAR1 和突触素（SYN）mRNA 和蛋白的表达。rTMS 治疗后，VaD 大鼠的学习记忆能力明显提高，海马 CA1 区突触的超微结构得到重建。低频 rTMS 组和高频 rTMS 组大鼠海马 CA1 区 BDNF、NMDAR1 和 SYN 的 mRNA 和蛋白表达均高于 VaD 模型组（P＜0.05）。rTMS 在血管性痴呆的修复治疗中发挥着重要而有益的作用，这可能与 rTMS 能增加 BDNF、NMDAR1 和 SYN 的 mRNA 和蛋白表达，影响海马 CA1 区的突触可塑性有关。
