Sex-specific expression of BDNF and CART in the midbrain non-preganglionic Edinger–Westphal nucleus in the rat

In mammals, females generally appear more vulnerable to stressors than males. The non-preganglionic Edinger–Westphal nucleus (npEW) has been implicated in regulation of the stress response. Brain-derived neurotrophic factor (BDNF) and cocaine- and amphetamine-related transcript peptide (CART) are sex-specifically involved in the stress response too, and are present in the human and rat npEW. We hypothesized that male and female rats would differ in the expression of BDNF and CART in the npEW. Using immunocytochemistry and in situ hybridization we found that BDNF, CART and the estrogen receptor β (ERβ) are colocalized in the npEW. Q-RT-PCR showed no differences in CART and BDNF coding mRNAs between males and females, but quantitative immunocytochemistry revealed a 16% lower number of BDNF-immunoreactive neurons, and 19% lower CART-immunoreactivity in females compared to males. Considering the fact that Ucn1, CART and BDNF are co-expressed in the npEW with ERβ and their protein expression differs between males and females, we propose that the functioning of the npEW may contribute to the sex differences that exist in stress sensitivity.