| Popis: |
Mutations in gene IGSF9B are heavily associated with negative and cognitive, but not positive symptoms of schizophrenia (SZ). Gene IGSF9B encodes for Immunoglobulin Superfamily Member 9b (IgSF9b), a cell adhesion molecule expressed at inhibitory synapses that regulates inhibitory synapse formation and transmission. IgSF9b is heavily expressed in the medial prefrontal cortex (mPFC), an area responsible for higher executive functioning which is disrupted in SZ. Whether IgSF9b deficiency, specifically within the mPFC, affects mPFC-associated behaviors remain unexplored. To that end, we specifically knocked down (KD) IgSF9b levels in the mPFC of young adult mice utilizing short hairpin RNA (shRNA) virus. Our results showed that IgSF9b deficiency in the mPFC disrupted working memory performance and produced sociability deficits, primarily affecting female, but not male, mice. Further, we analyzed spine density and synaptic protein levels in IgSF9b KD female mice. Although total spine density was not affected, we found an aberration in stubby spine density in apical dendrites of layer II/III pyramidal neurons in the mPFC of IgSF9b KD female mice. Additionally, there was a significant decrease in N-methyl-D-aspartic acid receptor (NMDAR) GluN1, but not GluN2A and GluN2B, subunit levels in the mPFC of IgSF9b KD female mice. Our study, for the first time, investigated the behavioral, cellular, and molecular effects of IgSF9b deficiency in the mouse mPFC and its potential association in the pathogenesis of social and cognitive deficits in SZ. |
