PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

Experimental Neurology
Isabel Vieira de Assis LimaAntonio Carlos Pinheiro de Oliveira

Abstract

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 PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ(-/-)) subjected to intrahippocampal microinjection of pilocarpine. PI3Kγ(-/-) mice presented a more severe status epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or pharmacological blockade of PI3Kγ 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 PI3Kγ(-/-) animals after the induction of SE. Levels of BDNF were significantly increased in the hippocampus of WT and PI3Kγ(-/-) mice, although in the prefrontal cortex, only PI3Kγ(-/-) 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 pr...Continue Reading

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Citations

May 5, 2016·Scientific Reports·Paula Maria Quaglio BelloziAntônio Carlos Pinheiro de Oliveira
Nov 13, 2020·Frontiers in Neuroscience·Dong Hyeon KangSang Won Suh
Sep 22, 2019·Neuropharmacology·Paula Maria Quaglio BelloziAntônio Carlos Pinheiro de Oliveira
Jun 24, 2020·Neuropharmacology·Isabel Vieira de Assis LimaAntônio Carlos Pinheiro de Oliveira
May 13, 2021·Neuroscience Letters·Érica Leandro Marciano VieiraAntônio Carlos Pinheiro de Oliveira

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