Mice presenting a schizophrenia-like phenotype show alterations in maturation of perineuronal nets.

PRETELL ANNAN, CARLOS A; BELFORTE JE

Mar del Plata

Congreso; Reunion Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2017

Sociedad Argentina de Investigación en Neurociencias (SAN)

Although the etiology of schizophrenia is not known, cortical GABAergic interneuronsexpressing the calcium-binding protein parvalbumin (PVs) have been implicated in itspathophysiology: levels of GAD67 and PV have consistently been found to be decreased inhuman postmortem brain studies. Furthermore, perineuronal nets (PNNs) have also beenshown to be diminished in brain tissue from schizophrenic patients especially in PVs. PNNs ?reticular structures of extracellular matrix that surround the soma and proximal dendrites ofmany neurons in the CNS, including PVs ? are reportedly involved in synapse formation andstabilization.Given that normal wiring of cortical circuits relies on the proper maturation of PVs during thepostnatal period, and considering the neurodevelopmental aspect of schizophrenia, wehypothesized that an unsatisfactory formation of PNNs in early adulthood could be related tothe onset of the disease. In order to address this, we resorted to an NMDA receptor knockoutmouse model of schizophrenia and performed immunofluorescent stainings against PV andPNNs in young and adult mice, focusing in the medial prefrontal cortex. We found nodifferences in PNNs among asyntomatic pre-adolescent animals, but adult KO mice showed agreater percentage of PVs not enwrapped by PNNs when compared to adult controls. Thus,we conclude that the unsatisfactory maturation of PNNs during adolescence could bepathogenetically relevant for the emergence of the altered state