{"title":"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","authors":"Zahra Ebrahimi , Parsa Gholipour , Reihaneh Mohammadkhani , Reza Ghahremani , Abdolrahman Sarihi , Alireza Komaki , Iraj Salehi , Seyed Asaad Karimi","doi":"10.1016/j.ibneur.2024.05.005","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":13195,"journal":{"name":"IBRO Neuroscience Reports","volume":"16 ","pages":"Pages 629-634"},"PeriodicalIF":2.0000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667242124000502/pdfft?md5=52e9e71ff0c5c6d6687ddfc23f3f6062&pid=1-s2.0-S2667242124000502-main.pdf","citationCount":"0","resultStr":"{\"title\":\"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\",\"authors\":\"Zahra Ebrahimi , Parsa Gholipour , Reihaneh Mohammadkhani , Reza Ghahremani , Abdolrahman Sarihi , Alireza Komaki , Iraj Salehi , Seyed Asaad Karimi\",\"doi\":\"10.1016/j.ibneur.2024.05.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p></div>\",\"PeriodicalId\":13195,\"journal\":{\"name\":\"IBRO Neuroscience Reports\",\"volume\":\"16 \",\"pages\":\"Pages 629-634\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-05-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2667242124000502/pdfft?md5=52e9e71ff0c5c6d6687ddfc23f3f6062&pid=1-s2.0-S2667242124000502-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IBRO Neuroscience Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2667242124000502\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"IBRO Neuroscience Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667242124000502","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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
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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