Ebrahimi Zahra, Gholipour Parsa, Mohammadkhani Reihaneh, Ghahremani Reza, Sarihi Abdolrahman, Komaki Alireza, Salehi Iraj, Karimi Seyed Asaad
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran.
IBRO Neurosci Rep. 2024 May 22;16:629-634. doi: 10.1016/j.ibneur.2024.05.005. eCollection 2024 Jun.
The precise cause of autism spectrum disorder (ASD) is not fully understood. Despite the involvement of glutamatergic dysregulation in autism, the specific contribution of mGlu4 receptors to synaptic plasticity remains unclear. Using the positive allosteric modulator VU0155041, we aimed to restore long-term potentiation (LTP) in the perforant path-dentate gyrus (PP-DG) pathway in VPA-induced autistic rat model. High-frequency stimulation was applied to the PP-DG synapse to induce LTP, while the VU0155041 was administered into the DG. Unexpectedly, VU0155041 failed to alleviate the observed LTP reduction in VPA-exposed rats, further resulting in a significant decrease in population spike LTP. This unexpected outcome prompts discussion on the complex nature of mGlu4 receptor modulation, highlighting potential interference with physiological processes underlying synaptic plasticity.
自闭症谱系障碍（ASD）的确切病因尚未完全明确。尽管谷氨酸能调节异常与自闭症有关，但代谢型谷氨酸受体4（mGlu4）对突触可塑性的具体作用仍不清楚。我们使用正变构调节剂VU0155041，旨在恢复丙戊酸（VPA）诱导的自闭症大鼠模型中穿通通路-齿状回（PP-DG）通路的长时程增强（LTP）。对PP-DG突触施加高频刺激以诱导LTP，同时将VU0155041注入齿状回。出乎意料的是，VU0155041未能缓解VPA暴露大鼠中观察到的LTP降低，反而导致群体峰电位LTP显著下降。这一意外结果引发了对mGlu4受体调节复杂性的讨论，突出了对突触可塑性潜在生理过程的干扰。
