Injury-induced and sexually dimorphic patterns of aromatase and bone morphogenetic protein-2 expression in the adult zebra finch brain.

摘要

Songbirds are powerful models for the study of neuroplasticity. In the zebra finch, traumatic brain injury results in the local upregulation of the estrogen synthetic enzyme aromatase. Inhibition of this glial aromatase results in increased degeneration and cell death, suggesting estrogen mediated neuroprotection. However, the full impact of this aromatase upregulation on the injured brain has yet to be characterized. Experiments were conducted to determine whether or not injury-induced aromatase affects neurogenesis or the expression of bone morphogenetic proteins (BMPs). Inhibition of local aromatase via the drug Fadrozole did not reveal any increases in neurogenesis at 2 weeks following injury, though intracerebral administration of estradiol did. Injury resulted in increased local expression of BMPs 2 and 4, though only BMP2 was downregulated by Fadrozole treatment. Subsequently, experiments were conducted to determine whether or not the global expression of aromatase and/or BMP2 differed in response to injury or across survival times post-insult, and immunocytochemistry was used to investigate the distribution of BMP2 expression within the injured zebra finch brain. Global aromatase expression actually decreased, while BMP2 expression in contralateral, uninjured hemispheres increased, with time post-injury. Immunocytochemistry against BMP2 revealed widespread expression in the adult zebra finch brain, with more expression in the medial striatum of males compared to females, and greater expression around the injury site as compared corresponding tissue in uninjured hemispheres. Additionally, BMP2 expressing cells throughout the telencephalon were almost entirely neuronal, while BMP2 expressing cells around injury were positive for the pan-macrophage protein macrosialin (a.k.a. CD68). Together, the results presented here suggest that BMP2 and aromatase are both widely and differentially expressed, and therefore may be involved in several processes mediating the response to injury, in the adult zebra finch brain. Hypotheses are discussed concerning the potential involvement of BMP2 in processes of neuroinflammation, gliosis, neuroprotection, and neuroplasticity.