Sex-dependent expression of N-cadherin-GluA1 pathway-related molecules in the prefrontal cortex mediates anxiety-like behavior in male offspring following prenatal stress

Prenatal stress (PS) affects neurodevelopment and increases the risk for anxiety in adolescence in male offspring, but the mechanism is still unclear. N-Cadherin regulates the expression of AMPA receptors (AMPARs), which mediate anxiety by modulating network excitability in the prefrontal cortex (PFC). Our results revealed that in adolescent male, but not female, offspring rats, PS induced anxiety-like behavior, as assessed by the open field test (OFT). Furthermore, N-cadherin and AMPAR subunit GluA1 were colocalized in the PFC, and the expression of the N-cadherin and the GluA1 decreased following PS exposure in male offspring rats. We also found that the AMPAR agonist CX546 did not alleviate anxiety-like behavior in adolescent male offspring rats; however, it increased the expression of GluA1 in the PFC but did not alter the expression of N-cadherin. In conclusion, our study suggested that the N-cadherin-GluA1 pathway in the PFC mediates anxiety-like behavior in adolescent male offspring rats and that N-cadherin might be required for sex differences in the effect of PS on adolescent offspring.