Estrogen provision by reactive glia decreases apoptosis in the zebra finch (Taeniopygia guttata).
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.
Saldanha
Colin J
CJ
Department of Biological Sciences, Lehigh University, 111 Research Drive, Bethlehem, Pennsylvania 18015, USA. colin@lehigh.edu
Rohmann
Kevin N
KN
Coomaralingam
Luckshman
L
Wynne
Ryan D
RD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001141:Aromatase / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count / Q000379:methods; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000009:adverse effects; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D017316:Fadrozole / Q000009:adverse effects; D046369:Finches; D005452:Fluoresceins; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009930:Organic Chemicals; D014746:Vimentin / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D005452:Fluoresceins; D009930:Organic Chemicals; D014746:Vimentin; C435731:fluoro jade; D001141:Aromatase; D017316:Fadrozole