A major role for astrocytes in the neuroprotective effect of estrogen

Abstract

Estrogen exerts neurotrophic and neuroprotective activity as suggested by both in vitro and in vivo evidence. Expression of estrogen receptors has been demonstrated in neurons and also in glial cells. Glia, and in particular astrocytes, represent a target for estrogen and contribute to the neuroprotective effect of the steroid hormone. Particular emphasis is given here to the role of astrocytes in mediating some of the protective effects of estrogen in models of neuronal damage. Estrogen receptors are up-regulated in different brain areas during neurodegeneration, a phenomenon that may potentiate neuroprotective mechanisms, and estrogen appears effective in modulating the uptake of the excitotoxin glutamate. In addition, following neuronal insults, astrocytes may represent a source of estrogen through overexpression of the estrogen-synthesizing enzyme, aromatase. The contribution of astrocytes as a source of growth factors is also discussed in terms of the neuroprotection obtained in different in vitro models of neurodegenerative conditions. Drug Dev. Res. 66:126-135, 2006.

Estrogen receptor-α is localized to neurofibrillary tangles in Alzheimer’s disease

“…3D ). This staining pattern has been demonstrated in rat brain 50 51 and thus the similar finding here in human brain further confirms the specificity of the antibody. It has been reported that ERα is present in glial cells 52 , and indeed throughout the hippocampus in all cases of both AD and control groups used in this study, small nuclei were readily stained for ERα, representing a glial cell population (arrowheads, Fig.…”

Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice

“…Ironically, expression levels of ERs are elevated in astrocytes of the ventral spinal cord in ALS patients [45]. Therefore, it is likely that estrogen may function indirectly through astrocytes [45][46][47]. Indeed, E2 increases synthesis, production, and release of glial derived neurotrophic factor (GDNF) [48].…”

The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival

“…However, indirect observations suggest that astrocytes may help augment pericyte proliferation through augmentation of PDGFβ levels [ 165 ] or release of inflammatory mediators [ 166 ] that enhance gliosis. In patients with glaucoma, enhanced proliferation is modest but restricted to NG2+ pericytes [ 167 ]. Astrocytes and pericytes both express estrogen receptors [ 167 - 169 ].…”

“…In patients with glaucoma, enhanced proliferation is modest but restricted to NG2+ pericytes [ 167 ]. Astrocytes and pericytes both express estrogen receptors [ 167 - 169 ]. Astrocytes have been shown to be a source of estrogen following neuronal injury due to an upregulation of aromatase [ 167 ].…”