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

Isabel Vieira de Assis Lima, Alline Cristina Campos, Aline Silva Miranda, Érica Leandro Marciano Vieira, Flávia Amaral-Martins, Juliana Priscila Vago, Rebeca Priscila de Melo Santos, Lirlândia Pires Sousa, Luciene Bruno Vieira, Mauro Martins Teixeira, Bernd L. Fiebich, Márcio Flávio Dutra Moraes, Antonio Lucio Teixeira, Antonio Carlos Pinheiro de Oliveira

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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 prefrontal cortex this increase was observed only in PI3Kγ-/- mice. Regarding the levels of inflammatory mediators, pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and PI3Kγ-/- animals and in the prefrontal cortex of PI3Kγ-/- animals 24h after the stimulus. Levels of TNFα were enhanced in the hippocampus and prefrontal cortex of only PI3Kγ-/- mice at this time point. On the other hand, PI3Kγ deletion impaired the increase in IL-10 in the hippocampus induced by pilocarpine. In conclusion, the lack of PI3Kγ 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.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalExperimental Neurology
StatePublished - May 1 2015
Externally publishedYes


  • Cytokines
  • Glutamate
  • Microglia
  • Neurodegeneration
  • Neurotrophins
  • Phosphatidylinositol 3-kinase
  • Pilocarpine
  • Seizures

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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