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低频重复经颅磁刺激可减轻丙戊酸诱导的小鼠模型中的社交障碍。

Low-frequency RTMS attenuates social impairment in the VPA-induced mouse model.

作者信息

Wang Xinyi, Li Yanna, Li Rui, Yuan Linying, Hua Yanfan, Cai Yulong, Liu Xinfeng

机构信息

Department of Neurology, Affiliated Jinling Hospital, Medical School, Nanjing University, Nanjing, Jiangsu 210000, China.

Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Behav Brain Res. 2024 Aug 24;472:115156. doi: 10.1016/j.bbr.2024.115156. Epub 2024 Jul 19.

Abstract

BACKGROUND

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. Despite its prevalence, effective treatments remain elusive. Recent studies have highlighted the importance of the balance between GABAergic and glutamatergic neuronal synaptic functions in ASD development. Repetitive transcranial magnetic stimulation (RTMS) is a painless and effective treatment allowed for use in depression and obsessive-compulsive disorder. However, its efficacy in treating autism is still under investigation. Low-frequency RTMS (LF-RTMS), which shows promise in reducing autism-like behaviors, is considered to regulate synaptic function.

OBJECTIVE

We observed and recorded the behaviors of mice to assess the impact of RTMS on their social interactions and repetitive activities. Subsequently, we examined GABAergic and glutamatergic neuronal markers along with synaptic marker proteins to understand the underlying changes associated with these behaviors.

METHODS

To evaluate behaviors associated with autism spectrum disorder (ASD), several behavioral tests were conducted, focusing on sociability, repetitive behaviors, locomotion, anxiety, and depression. Additionally, Western blot and immunofluorescence staining were employed to investigate the activity of GABAergic and glutamatergic neurons in the hippocampus, aiming to understand the synaptic mechanisms underlying these behaviors.

RESULTS

LF-RTMS treatment effectively relieved the social disability and normalized synaptic function in the hippocampus of ASD mice model induced by valproate (VPA). Importantly, this treatment did not lead to any adverse effects on repetitive behavior, locomotion, anxiety, or depression.

CONCLUSION

LF-RTMS attenuated social disability without affecting repetitive behavior, locomotion, anxiety, or depression. Changes in the expression of GABAergic and glutamatergic neuronal synaptic proteins in the hippocampus were also observed.

摘要

背景

自闭症谱系障碍(ASD)是一种神经发育障碍,其特征为社交互动受损和重复行为。尽管其患病率较高,但有效的治疗方法仍然难以捉摸。最近的研究强调了γ-氨基丁酸能(GABAergic)和谷氨酸能神经元突触功能平衡在ASD发展中的重要性。重复经颅磁刺激(RTMS)是一种可用于治疗抑郁症和强迫症的无痛且有效的治疗方法。然而,其治疗自闭症的疗效仍在研究中。低频RTMS(LF-RTMS)有望减少自闭症样行为,被认为可调节突触功能。

目的

我们观察并记录小鼠的行为,以评估RTMS对其社交互动和重复活动的影响。随后,我们检测了GABA能和谷氨酸能神经元标志物以及突触标志物蛋白,以了解与这些行为相关的潜在变化。

方法

为评估与自闭症谱系障碍(ASD)相关的行为,进行了多项行为测试,重点关注社交性、重复行为、运动、焦虑和抑郁。此外,采用蛋白质免疫印迹法和免疫荧光染色法研究海马中GABA能和谷氨酸能神经元的活性,旨在了解这些行为背后的突触机制。

结果

LF-RTMS治疗有效缓解了丙戊酸(VPA)诱导的ASD小鼠模型海马中的社交障碍并使突触功能正常化。重要的是,这种治疗对重复行为、运动、焦虑或抑郁没有产生任何不良影响。

结论

LF-RTMS减轻了社交障碍,而不影响重复行为、运动、焦虑或抑郁。还观察到海马中GABA能和谷氨酸能神经元突触蛋白表达的变化。

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