Anales RANF

P.50 A POSSIBLE IMPLICATION OF THE ATP-GATED P2X7 RECEPTOR ON STATUS EPILEPTICUS-INDUCED A BERRANT NEUROGENESIS G. de Leo 1 , E. Beamer 1 , T.Engel 1 1 Royal College of Surgeons in Ireland, Dublin, Ireland New neurons are generated continuously during the entire lifespan in the adult brain of mammals, including humans. Neurogenesis occurs in the subventricular zone, in the walls of the lateral ventricles, and the subgranular zone, in the dentate gyrus of the hippocampus, the two main adult neurogenic niches. This physiological process is upregulated following acute insult, such as status epilepticus, traumatic brain injury or stroke. Emerging data has demonstrated a prominent role of extracellular ATP in regulating neurogenesis. While P2X7 has been shown to alter the rate of neurogenesis, however, whether P2X7 also alters status epilepticus-induced neurogenesis has not been fully addressed. Using an intra amygdala kainic acid mouse model of status epilepticus, in a transgenic mouse overexpressing P2X7 receptor, we used immunohistochemistry to visualize changes in the distribution of markers of neuronal development (e.g. Nestin, Doublecortin, NeuN) and trackers such as Iodo/Chloro-deoxyuridine (IdU/CldU), injected respectively 3 days and 17 days after the kainic acid injection. The rate of neurogenesis in the dentate gyrus is increased in kainic acid-injected mice, with an evident presence of newly generated neurons, with a noticeable change in morphology, and located ectopically in the hilus. P2X7 overexpression increased not only the number of trackers positive cells in the subgranular zone and in the granular layer of the hippocampus, but also on status epilepticus-induced aberrant neurogenesis with several cells detected in the hilus. In conclusion, using this animal model of epilepsy together with genetic manipulation permitted to investigate the involvement of P2X7 receptor in aberrant neurogenesis following status epilepticus.

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