State Key Laboratory of Reliability and Intelligence of Electrical Equipment, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, 300130 Tianjin, China; College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071 Tianjin, China.
College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, 300071 Tianjin, China.
Pharmacol Biochem Behav. 2024 Jul;240:173788. doi: 10.1016/j.pbb.2024.173788. Epub 2024 May 9.
Autism is a complex neurodevelopmental disorder with no effective treatment available currently. Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising neuromodulation technique to treat autism. However, the mechanism how rTMS works remains unclear, which restrict the clinical application of magnetic stimulation in the autism treatment. In this study, we investigated the effect of low-frequency rTMS on the autistic-like symptoms and explored if this neuroprotective effect was associated with synaptic plasticity and neuroinflammation in the hippocampus. A rat model of autism was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats and male offspring were treated with 1 Hz rTMS daily for two weeks continuously. Behavior tests were performed to identify behavioral abnormality. Synaptic plasticity was measured by in vivo electrophysiological recording and Golgi-Cox staining. Synapse and inflammation associated proteins were detected by immunofluorescence and Western blot analyses. Results showed prenatal VPA-exposed rats exhibited autistic-like and anxiety-like behaviors, and cognitive impairment. Synaptic plasticity deficits and the abnormality expression of synapse-associated proteins were found in the hippocampus of prenatal VPA-exposed rats. Prenatal VPA exposure increased the level of inflammation cytokines and promoted the excessive activation of microglia. rTMS significantly alleviated the prenatal VPA-induced abnormalities including behavioral and synaptic plasticity deficits, and excessive neuroinflammation. TMS maybe a potential strategy for autism therapy via rescuing synaptic plasticity and inhibiting neuroinflammation.
自闭症是一种复杂的神经发育障碍，目前尚无有效的治疗方法。重复经颅磁刺激(rTMS)作为一种有前途的神经调节技术，正被用于治疗自闭症。然而，rTMS 的作用机制尚不清楚，这限制了磁刺激在自闭症治疗中的临床应用。在这项研究中，我们研究了低频 rTMS 对自闭症样症状的影响，并探讨了这种神经保护作用是否与海马突触可塑性和神经炎症有关。通过给怀孕的大鼠腹腔注射丙戊酸(VPA)建立自闭症大鼠模型，雄性后代每天接受 1Hz rTMS 连续治疗两周。通过行为测试来识别行为异常。通过在体电生理记录和高尔基染色来测量突触可塑性。通过免疫荧光和 Western blot 分析检测突触和炎症相关蛋白。结果表明，产前 VPA 暴露的大鼠表现出自闭症样和焦虑样行为以及认知障碍。在产前 VPA 暴露的大鼠海马体中发现了突触可塑性缺陷和突触相关蛋白的异常表达。产前 VPA 暴露增加了炎症细胞因子的水平，并促进了小胶质细胞的过度激活。rTMS 显著缓解了产前 VPA 引起的异常，包括行为和突触可塑性缺陷以及过度的神经炎症。rTMS 可能是一种通过挽救突触可塑性和抑制神经炎症来治疗自闭症的潜在策略。
