| First Author | Lima IV | Year | 2015 |
| Journal | Exp Neurol | Volume | 267 |
| Pages | 123-34 | PubMed ID | 25749189 |
| Mgi Jnum | J:318250 | Mgi Id | MGI:6858919 |
| Doi | 10.1016/j.expneurol.2015.02.021 | Citation | Lima IV, et al. (2015) PI3Kgamma deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine. Exp Neurol 267:123-34 |
| abstractText | Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kgamma on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kgamma(-/-)) subjected to intrahippocampal microinjection of pilocarpine. PI3Kgamma(-/-) mice presented a more severe status epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or pharmacological blockade of PI3Kgamma enhanced the release of glutamate and the cytosolic calcium concentration induced by KCl. There was an enhanced neuronal death and a decrease in the doublecortin positive cells in the dentate gyrus of PI3Kgamma(-/-) animals after the induction of SE. Levels of BDNF were significantly increased in the hippocampus of WT and PI3Kgamma(-/-) mice, although in the prefrontal cortex, only PI3Kgamma(-/-) animals showed significant increase in the levels of this neurotrophic factor. Pilocarpine increased hippocampal microglial immunolabeling in both groups, albeit in the prelimbic, medial and motor regions of the prefrontal cortex this increase was observed only in PI3Kgamma(-/-) mice. Regarding the levels of inflammatory mediators, pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and PI3Kgamma(-/-) animals and in the prefrontal cortex of PI3Kgamma(-/-) animals 24h after the stimulus. Levels of TNFalpha were enhanced in the hippocampus and prefrontal cortex of only PI3Kgamma(-/-) mice at this time point. On the other hand, PI3Kgamma deletion impaired the increase in IL-10 in the hippocampus induced by pilocarpine. In conclusion, the lack of PI3Kgamma revealed a deleterious effect in an animal model of convulsions induced by pilocarpine, suggesting that this enzyme may play a protective role in seizures and pathological outcomes associated with this condition. |
