Effect of intrahippocampal microinjection of VU0155041, a positive allosteric modulator of mGluR4, on long term potentiation in a valproic acid-induced autistic male rat model

IF 2 Q3 NEUROSCIENCES IBRO Neuroscience Reports Pub Date : 2024-05-22 DOI:10.1016/j.ibneur.2024.05.005

Zahra Ebrahimi , Parsa Gholipour , Reihaneh Mohammadkhani , Reza Ghahremani , Abdolrahman Sarihi , Alireza Komaki , Iraj Salehi , Seyed Asaad Karimi

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Abstract

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.

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在丙戊酸诱导的雄性自闭症大鼠模型中，海马内显微注射 mGluR4 的正异位调节剂 VU0155041 对长期电位的影响

自闭症谱系障碍（ASD）的确切病因尚不完全清楚。尽管自闭症涉及谷氨酸能失调，但 mGlu4 受体对突触可塑性的具体贡献仍不清楚。我们使用正性异位调节剂 VU0155041，旨在恢复 VPA 诱导的自闭症大鼠穿孔路径-齿状回（PP-DG）通路的长期电位（LTP）。对 PP-DG 突触施加高频刺激以诱导 LTP，同时将 VU0155041 注入 DG。出乎意料的是，VU0155041未能缓解观察到的VPA暴露大鼠的LTP下降，进一步导致群体尖峰LTP显著下降。这一意想不到的结果引发了对 mGlu4 受体调节复杂性的讨论，突出了对突触可塑性基础生理过程的潜在干扰。

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