Expression of glial CBP in steroid mediated neuroprotection in male and female zebra finches.

Under neurodegenerative conditions, reactive astrocytes upregulate both aromatase (estrogen synthase) as well as estrogen and androgen receptors. This increased steroidogenic signal promotes neuroprotection and repair by promoting neurogenesis and decreasing cell death, but also by modulating the release of inflammatory molecules. Thus, endocrine - immune cross-talk is an essential component of estrogen mediated neuroprotection following brain injury. However, the exact mechanisms underlying this cross-talk remains unknown. cAMP response element-binding protein-binding protein (CBP) may be involved in the modulation of both the endocrine and inflammatory response following injury. CBP acts as both an estrogen receptor (ER) coactivator and as a promotor for NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) target genes and previous data suggests that ER and NF-κB compete for CBP. When CBP is displaced, target genes for NF-κB are repressed and inflammation is decreased. To test the role of CBP following injury, we examined CBP expression following penetrating injury in adult male and female zebra finches. Using immunohistochemistry, we were able to specifically examine glial CBP expression, as glial cells are important mediators of the neuroendocrine response to damage. Male but not female zebra finches upregulated glial CBP following damage to the brain. To determine if this upregulation was estrogen dependent, we decreased local estrogen levels with fadrozole (aromatase inhibitor) and reexamined glial CBP expression following injury. Aromatase inhibition resulted in no change in overall glial CBP expression suggesting that circulating estrogens do not mediate the upregulation of glial CBP following injury. Thus CBP may play a role in the both the estrogen and immune response to injury.