Parvalbumin and anxiety across development in female offspring of the MAM neurodevelopmental model of schizophrenia.

Schizophrenia is a neurodevelopmental disorder often accompanied by heightened anxiety. The methylazoxymethanol acetate (MAM) rodent model has demonstrated that prenatal MAM exposure disrupts neurodevelopment and leads to schizophrenia-like deficits, including increased anxiety-like behaviors. While previous research has focused primarily on male subjects, this study investigates anxiety-like behaviors and parvalbumin (PV) interneuron and perineuronal net (PNN) expression in the basolateral amygdala (BLA), thalamic reticular nucleus (TRN), and ventral hippocampus (vHIP) in female MAM rats across postnatal development (PD31-PD75). We found that female MAM rats exhibited increased anxiety-like behaviors in adulthood (PD75), as evidenced by reduced time spent and entries in the open arms of the elevated plus maze and increased center exploration in the open field test. At PD31, an increase in the open arms time and margin exploration was observed in female MAM rats. Interestingly, a baseline hyperlocomotion was observed at PD31 and PD51 in the MAM condition. The TRN also showed reduced PNN density at PD31 and PV density at PD51 which indicates a possible deficit in inhibitory control. Interestingly, in contrast to prior work in males, the BLA did not show alterations in PV or PNN densities that would contribute to increased anxiety, suggesting a different mechanism of anxiety regulation in females compared to males. These findings highlight sex-specific neurodevelopmental alterations following prenatal MAM exposure, emphasizing the need for further research on female models of schizophrenia. Understanding these differences may improve targeted therapeutic strategies for anxiety and psychosis risk in schizophrenia.