Anales RANF

P.61 DENDRITIC OUTGROWTH ALTERATIONS DURING THE PATHOGENESIS OF SCHIZOPHRENIA IN GENETIC MOUSE MODELS OF P2X7R P. Mut-Arbona 1 , B. Sperlágh 1 . 1 Institute of Experimental Medicine, Hungarian Academy of Sciences (IEM HAS), H- 1450 Budapest, Hungary. Neurons in some regions of the brain affected in schizophrenia (SCZ) show reduced dendritic length (Kalus et al. 2000) suggesting an abnormal dendritic outgrowth in schizophrenic patients. Correlation of abnormal dendritogenesis and human pathologies may offer some understanding to these currently untreatable diseases. P2x7 receptors (P2X7Rs) are potential therapeutic targets in SCZ. Genetic deficiency and pharmacological blockade of P2X7Rs shown to attenuate schizophrenia-like behaviour in rodents (Koványi et al., 2016). Our objective was to determine the regulation of neuronal outgrowth by P2X7Rs and the morphological correlates of P2X7R in primary cultures of murine hippocampal neurons derived from conventional wild-type (P2rx7+/+) and P2X7 receptor knockout (P2rx7 −/−) mice in an animal model of SCZ. Primary hippocampal neurons from P2X7R wildtype and knockdown mice obtained from E17.5–E18.5 embryos were dissected and processed. At day in vitro 10, transfection with GFP plasmid allows a clear visualization of the morphology of individual neurons in order to perform Neurolucida Software. Immunocytochemistry for the strengthening of the transfection was performed. One and Two-way ANOVA were used to determine statistically significant differences in the Sholl analyses, depending on the needs. All data are presented as mean ± SEM. Deficits in dendritic outgrowth have been reported in P2X7R deficient mice, but also, in primary hippocampal neurons from wild-type animals co-cultured with P2X7R antagonist in a dose dependent manner. In conclusion, P2X7R depletion led to abnormal dendritic arborization in primary hippocampal neurons, demonstrating that P2X7R is needed for normal dendritic outgrowth during neuronal development, proliferation and maturation. The dendritic deficits in the disease model could constitute good correlates of the cognitive deficits in the schizophrenia. Additional genetic approaches should be tested to analyze and rescue these morphological deficits.