Neuropharmacology

Biography

Biography: Marie-Françoise SUAUD-CHAGNY

Abstract

MAP6 (microtubule-associated protein 6) KO mouse is a microtubule-deficient model that exhibits severe behavioural and biological alterations reminiscent of schizophrenia. Total deletion of MAP6 gene in mice leads, in adulthood, to behavioural disorders related to positive and negative symptoms and to cognitive impairments seen in schizophrenia. The strong behavioural phenotype of MAP6-KO mice may be the consequence of the many biological dysfunctions seen in these mice and known to be implicated in schizophrenia, such as nervous system plasticity impairments and alterations in many neurotransmission systems. Some of these behavioural and biological defects are sensitive to antipsychotics but also to microtubule-modulator molecules. A decreased expression of MAP6 proteins in heterozygous (Het) mice results in a blunted phenotype compared to MAP6-KO mice, corroborating that the dosages of susceptibility genes modulate their putative phenotypic contribution. Het mice displayed behavioural deficits strongly arguing for a high penetrance of MAP6 mutation in cognition. Human studies propose cognitive deficits in ultra-high-risk populations as robust premorbid predictive markers of a subsequent psychotic disorder. We propose MAP6-Het mouse as a translational animal model for the genetic ultra-high-risk states of schizophrenia. The validity of the model is supported by the exacerbation, through maternal deprivation, of the behavioural alterations related to positive symptoms. Such a model will help to elucidate transition factors from ultra-high-risk states to full-blown psychosis and to decipher the mechanisms underlying this transition. Because cognitive deficits in ultra-high-risk populations have been proposed as targets for early intervention, MAP6-Het mice would be valuable tools to study preventive strategies.