Estrogen provision by reactive glia decreases apoptosis in the zebra finch (Taeniopygia guttata)

Abstract

Upregulation of aromatase (estrogen synthase) in glia around the site of neural injury may limit neural degeneration. Systemic administration of estrogen limits neural damage, but the specific role of local estrogen provision in this effect is unclear. In male zebra finches, we tested the effect of local aromatase inhibition and estrogen replacement on type of cellular degeneration and the distance of this degeneration from the source of insult. Subjects received injections of the aromatase inhibitor fadrozole into one telencephalic lobe and fadrozole and estradiol into the contralateral lobe. Seventy-two hours later, we used Fluoro-Jade B and TUNEL to label dying and apoptotic cells, respectively. Since each subject was its own control, we were able to assess the influence of local estrogen replacement in relative distinction from circulating steroids and constitutive aromatization. Cellular degeneration around the lesion was measured with Fluoro-Jade B, TUNEL, and indirectly with aromatase expression. Additionally, the glial nature of aromatase-positive cells around the injury was queried by co-localization with vimentin. The estrogen replaced injury had fewer apoptotic cells clustered more closely around the injury compared to the hemisphere injected with fadrozole alone. Since Fluoro-Jade B and TUNEL labeled similar numbers of cells, and the distance of these cells from the injection was identical, we suggest that estrogen replacement functions primarily to restrict apoptosis in the current paradigm. Lastly, aromatase-positive cells around injuries co-localize vimentin, establishing their glial nature. Thus, glial estrogen provision at sites of neural insult may be critical in limiting the cellular degeneration caused by injury via an inhibition of apoptosis.

Role of P450 Aromatase in Sex-Specific Astrocytic Cell Death

“…However, in a recent study by Yague et al (2006), it was shown that P450 aromatase is expressed in human brain in subpopulations of pyramidal neurons and astrocytes. Furthermore, as shown by Azcoitia et al (2003) and Saldanha et al (2005), P450 aromatase is induced in rat and zebra finch brain after injury in astrocytes. Finally, our study and that of others (Zwain and Yen, 1999;Schlinger et al, 1994) show that the P450 aromatase is expressed in astrocytes in culture without apparent injury.…”

Neurotrophic and neuroprotective actions of estrogen: Basic mechanisms and clinical implications

“…As mentioned previously, brain-derived estrogen may play an important role in protecting the brain, as evidenced by the aromatase mutant mouse studies described previously [28]. Astrocytes may participate in the production of brain-derived estrogen as they have been shown to express aromatase and this expression is enhanced following cerebral ischemia and following brain injury [31,91]. Thus, local production of estrogen by astrocytes could be another mechanism of astrocyte-mediated protection of neurons.…”

Rapid seasonal-like regression of the adult avian song control system

“…17␤-Estradiol (E 2 ), a metabolite of T, promotes the expression of several antiapoptotic genes (43)(44)(45)(46)(47)(48). In zebra finches, neuronal injury is accompanied by an increase in expression of aromatase, an enzyme that converts T to E 2 (49), and inhibition of aromatase increases apoptosis near the injury (50). These results suggest that T and/or its metabolites may reduce programmed cell death in HVC of songbirds.…”