Isabel Vieira de Assis Lima, Hyorrana Priscila Pereira Pinto, Paula Maria Quaglio Bellozi, Maria Carolina Machado da Silva, Luciano R Vilela, Fabrício A Moreira, Márcio Flávio Dutra Moraes, Antônio Carlos Pinheiro de Oliveira
{"title":"大麻二酚对戊四唑诱发癫痫发作的影响依赖于PI3K。","authors":"Isabel Vieira de Assis Lima, Hyorrana Priscila Pereira Pinto, Paula Maria Quaglio Bellozi, Maria Carolina Machado da Silva, Luciano R Vilela, Fabrício A Moreira, Márcio Flávio Dutra Moraes, Antônio Carlos Pinheiro de Oliveira","doi":"10.1007/s43440-022-00391-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).</p><p><strong>Methods: </strong>We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.</p><p><strong>Results: </strong>PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.</p><p><strong>Conclusion: </strong>Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.</p>","PeriodicalId":166986,"journal":{"name":"Pharmacological reports : PR","volume":" ","pages":"1099-1106"},"PeriodicalIF":0.0000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.\",\"authors\":\"Isabel Vieira de Assis Lima, Hyorrana Priscila Pereira Pinto, Paula Maria Quaglio Bellozi, Maria Carolina Machado da Silva, Luciano R Vilela, Fabrício A Moreira, Márcio Flávio Dutra Moraes, Antônio Carlos Pinheiro de Oliveira\",\"doi\":\"10.1007/s43440-022-00391-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).</p><p><strong>Methods: </strong>We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.</p><p><strong>Results: </strong>PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.</p><p><strong>Conclusion: </strong>Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.</p>\",\"PeriodicalId\":166986,\"journal\":{\"name\":\"Pharmacological reports : PR\",\"volume\":\" \",\"pages\":\"1099-1106\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacological reports : PR\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s43440-022-00391-y\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/9/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological reports : PR","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s43440-022-00391-y","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/16 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K.
Background: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).
Methods: We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.
Results: PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.
Conclusion: Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.
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