Bradley Walters - Injury and Glial Aromatization Combine to Upregulate Bone Morphogenic Protein 2 in the Adult Zebra Finch Brain

Bradley Walters
Department of Biological Sciences
Brain injury upregulates glial aromatase. The resulting local estrogen synthesis mitigates cell death and enhances cell proliferation by poorly understood mechanisms. Bone morphogenetic proteins (BMPs), well known for their roles in neural development, also promote cellular proliferation and survival. However, BMPs remain poorly characterized in the injured brain, as do the mechanisms regulating their post-injury expression. We first established the expression of BMPs 2, 4, 6, and 7 in the adult zebra finch brain by amplifying and sequencing the respective gene products. Next, we determined the effect of brain injury on BMP expression, by comparing the relative abundance of transcripts between injured and uninjured brain tissue. Brain damage increased the expression of BMPs 2 and 4, but not 6 and 7,when compared 24 hours after injury. To determine the influence of glial aromatase on BMP expression, we compared BMP levels following delivery of either fadrozole (an aromatase inhibitor) or saline into opposing hemispheres. Fadrozole decreased BMP2, but not BMP4, expression, suggesting that local aromatization contributes to the upregulation of BMP2 following injury.  Subsequently we compared the extent and distribution of BMP2 protein expression across injured and uninjured conditions as well as across sex.  BMP2 protein was detected in several brain areas, including areas critical to song learning and production.  Comparison of cell density measures suggest that BMP2 expression differs across brain areas and across sex.  Since BMPs have been shown to enhance neural cell proliferation and survival, future studies will test if the neuroprotective and cytogenic effects of aromatase upregulation are mediated by BMP2.  Additionally, as BMP2 has been implicated in cognitive function, the zebra finch is not only a powerful model for understanding the role(s) of BMP2 in brain repair, but may also provide new insights into the actions of BMP2 in learning and memory.
This project was funded by Lehigh University’s College of Arts and Sciences, and by the National Institutes of Health (NINDS 047267).
Brad Walters is a doctoral candidate in the Department of Biological Sciences at Lehigh University. He currently holds the Thorne Fellowship for Integrative Biology and was recently showcased in the departmental “student spotlight” ( Brad works in the laboratory of Dr. Colin Saldanha, where he studies the relationships between steroids and growth factors in the prevention of neuronal death and the facilitation of brain repair. Research in the Saldanha lab is funded by grants from Lehigh University’s College of Arts and Sciences and from the National Institutes of Health (NINDS 042767)