Estrogen mediation of injury‐induced cell birth in neuroproliferative regions of the adult zebra finch brain

Abstract

Estrogens influence neuronal differentiation, migration, and survival in intact brains. In injured brains, estrogens can also be neuroprotective. In Experiment 1, following a unilateral penetrating injury to the hippocampus (HP), adult female zebra finches were injected once with BrdU to label mitotic cells then sacrificed 2 h, 1 day, or 7 days postinjection. Cell proliferation was dramatically enhanced in the ipsilateral HP, as well as in neuroproliferative areas including the subventricular zone (SVZ) proximal to the injury. This increase was seen at all time points investigated. Ovariectomy (OVX) substantially suppressed proliferation bilaterally especially in the SVZ indicating that gonadal hormones influenced cell proliferation in both the intact and injured hemisphere. To determine if estrogens were directly involved, estrogen was depleted in Experiment 2 through either OVX or administration of the aromatase inhibitor fadrozole (FAD). Birds were implanted with estradiol or blank followed 2 weeks later by a unilateral penetrating lesion to the HP. Injury-induced substantial proliferation, which was again significantly suppressed bilaterally in both OVX and FAD birds. Estrogen replacement reversed this effect in FAD but not OVX birds therefore the suppression following OVX may be due in part to nonestrogenic influences. Suppression of cell birth in FAD birds was indeed due to the removal of endogenous sources of estrogen. Results therefore indicate that estrogens are directly involved in the brain's response to injury and may be acting to provide a rich environment for the production and perhaps protection of new cells.

A Quantification of the Injury‐Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch

“…Given previous studies establishing the involvement of the oestrogen receptors ERa, ERb and GPER-1 in neuroprotection following brain injury (15,16,(18)(19)(20)(22)(23)(24)(25)(26)(27), we were surprised to find no differences in the expression of these receptors in the present experiment. We did, however, observe a significant down-regulation of AR expression in the injured hemisphere compared to the uninjured hemisphere of both male and female zebra finches (Fig.…”

“…Similarly, administration of peripheral E 2 attenuates the increased neuronal damage induced by aromatase inhibition following injury in mice (17). In addition to the mitigation of neuronal damage and secondary degeneration following brain injury, E 2 has also been suggested to enhance neurogenesis after injury (18)(19)(20). The data strongly suggest that the neuroprotective effects of centrally synthesised E 2 are a conserved characteristic across several vertebrates.…”

Environmental Enrichment Rescues Postnatal Neurogenesis Defect in the Male and Female Ts65Dn Mouse Model of Down Syndrome

“…Therefore, it is likely that environmental enrichment and physical exercise together may increase cognitive ability in male Ts65Dn mice, which otherwise exhibit deteriorated cognitive function under standard enriched environment [34]. The distinctive early effect of enrichment and wheel running on female Ts65Dn SVZ proliferation and neurogenesis suggests a potential role of sex hormones such as estrogen on these cellular changes [54,55]. In fact, in animal models of brain injury, it has been shown that there is a gender-based difference in the response of SVZ cells on proliferation after the injury [56].…”

Estrogenic regulation of dopaminergic neurons in the opportunistically breeding zebra finch

“…Relative to other aromatase inhibitors, LET has been employed to only a limited extent in songbirds, and although we found clear evidence of its efficacy, the drug was not tolerated well in zebra finches at doses comparable to an orally administered aromatase inhibitor in a previous study [46]. However, LET appears to be more effective than another popular aromatase inhibitor, ATD, at least under certain experimental conditions [36,74].…”