Glial expression of estrogen and androgen receptors after rat brain injury

Abstract

Estrogens and androgens can protect neurons from death caused by injury to the central nervous system. Astrocytes and microglia are major players in events triggered by neural lesions. To determine whether glia are direct targets of estrogens or androgens after neural insults, steroid receptor expression in glial cells was assessed in two different lesion models. An excitotoxic injury to the hippocampus or a stab wound to the parietal cortex and hippocampus was performed in male rats, and the resultant expression of steroid receptors in glial cells was assessed using double‐label immunohistochemistry. Both lesions induced the expression of estrogen receptors (ERs) and androgen receptors (ARs) in glial cells. ERα was expressed in astrocytes immunoreactive (ERα‐ir) for glial fibrillary acidic protein or vimentin. AR immunoreactivity colocalized with microglial markers, such as Griffonia simplicifolia lectin‐1 or OX‐6. The time course of ER and AR expression in glia was studied in the stab wound model. ERα‐ir astrocytes and AR‐ir microglia were observed 3 days after lesion. The number of ERα‐ir and AR‐ir glial cells reached a maximum 7 days after lesion and returned to low levels by 28 days postinjury. The studies of ERβ expression in glia were inconclusive; different results were obtained with different antibodies. In sum, these results suggest that reactive astrocytes and reactive microglia are a direct target for estrogens and androgens, respectively. J. Comp. Neurol. 450:256–271, 2002. © 2002 Wiley‐Liss, Inc.

Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

“…Small, AR+ puncta were variable in number, but found in most brain regions that also contained nuclear AR. Based on size and distribution, these puncta may be glial cells or nerve terminals, both of which have been shown to contain ER or AR in other systems (e.g., Blaustein, 1992;Garcia-Ovejero et al, 2002;Wagner et al, 1998). In the absence of electron microscopy, however, we can only speculate as to what structures these puncta are associated with, and therefore restrict the remainder of our discussion to the more traditional, nuclear AR.…”

Neuroactive steroids, their metabolites, and neuroinflammation

“…In rats, for example, brain injury induces the expression of ERa in vimentin or glial fibrillary acidic protein (GFAP)-positive astrocytes and of AR in Griffonia simplicifolia lectin-1 or MHC-IIpositive microglia, suggesting that the expression of several receptors in different cell types is necessary for the correct modulation of the response to the insults (García-Ovejero et al 2002).…”

Estrogen Receptor Alpha Inhibits the Estrogen-Mediated Suppression of HIV Transcription in Astrocytes: Implications for Estrogen Neuroprotection in HIV Dementia

“…The increase in the ratio of ERa-IR astrocytes in the hippocampus of HAD patients may provide a desirable target for estrogen action. In support of this, an increase in ERa-IR astrocytes has been reported in the rat following a stab wound and excitotoxic injury 24 and estrogen has been shown to provide neuroprotection in both of these injuries. [53][54][55] Therefore, the fact that we did not observe the same trend in our HIV samples implies that ERa upregulation in astrocytes is not a general response to injury but appears to be injury specific.…”

“…22,35,45,46 ERa expression increases in reactive astrocytes in the rodent, primate, and human brain, 24,27 and In the absence of viral infection no HIV protein is found. As shown, the HIV þ brain contains 35 reactive astrocytes, 10 of which express ERa.…”

“…Indeed the protective effect of estrogen against ischemiainduced damage is dependent on the presence of estrogen receptor alpha (ERa). 22,23 Furthermore, astrocytes have been implicated in the neuroprotective effects of estrogen in the brain, [24][25][26] The fact that astrocyte expression of ERa is upregulated following injury to the rat, 24 primate, 27 and human brain 28 suggests a role for astrocyte-derived ERa in estrogenmediated neuroprotection. The present study was designed to investigate whether the E2-mediated suppression of Tat transactivation in astrocytes was dependent on the activation of estrogen receptors and, furthermore, to test whether ERa is upregulated in astrocytes in the HIV brain.…”