Astrocytes from acyclic female rats exhibit lowered capacity for neuronal differentiation

Lewis, Danielle K.; Woodin, Heather R.; Sohrabji, Farida

doi:10.1111/j.1474-9726.2008.00430.x

Cited by 8 publications

(6 citation statements)

References 66 publications

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“…Correspondingly, in vitro, only regular cyclers retained normal E2-dependent glial neurotrophic activity. These findings extend those of Lewis et al (26), which showed that astrocytes from 10-month-old acyclic rats had impaired neurotrophic activity with embryonic neural progenitor cells; however, this study did not distinguish ef- Figure 7. ER␣ and ER␤ expression in cerebral cortex astrocytes of perimenopausal female rats: influences of age and ovarian cycle status.…”

Section: Age Increase Of Astrocyte Er␣supporting

confidence: 85%

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neurotrophic Support in Male and Female Rats

et al. 2013

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Rodent models show decreased neuronal responses to estradiol (E2) during aging (E2-desensitization) in association with reduced neuronal estrogen receptor (ER)-α, but little is known about age changes of E2-dependent astrocytic neurotrophic support. Because elevated expression of astrocyte glial fibrillary acidic protein (GFAP) is associated with impaired neurotrophic activity and because the GFAP promoter responds to ERα, we investigated the role of astrocytic ERα and ERβ in impaired astrocyte neurotrophic activity during aging. In vivo and in vitro, ERα was increased greater than 50% with age in astrocytes from the cerebral cortex of male rats (24 vs 3 months), whereas ERβ did not change. In astrocytes from 3-month-old males, experimentally increasing the ERα to ERβ ratio induced the aging phenotype of elevated GFAP and impaired E2-dependent neurite outgrowth. In 24-month-old male astrocytes, lowering ERα reversed the age elevation of GFAP and partially restored E2-dependent neurite outgrowth. Mixed glia (astrocytes to microglia, 3:1) of both sexes also showed these age changes. In a model of perimenopause, mixed glia from 9- to 15-month rats showed E2 desensitization: 9-month regular cyclers retained young-like ERα to ERβ ratios and neurotrophic activity, whereas 9-month noncyclers had elevated ERα and GFAP but low E2-dependent neurotrophic activity. In vivo, ERα levels in cortical astrocytes were also elevated. The persisting effects of ovarian acyclicity in vitro are hypothesized to arise from steroidal perturbations during ovarian senescence. These findings suggest that increased astrocyte ERα expression during aging contributes to the E2 desensitization of the neuronal responses in both sexes.

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Section: Age Increase Of Astrocyte Er␣supporting

confidence: 85%

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neurotrophic Support in Male and Female Rats

et al. 2013

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“…As reported before, this method results in a typical cortical-striatal infarct common to MCAo models (Selvamani and Sohrabji, 2010a, 2010b). Astrocytes were harvested based on our previously published procedures (Lewis et al, 2008a, 2008b) and cultures were virtually pure for astrocytes (97%) as determined by GFAP immunohistochemistry, with low microglial contamination as determined by CD11b immunohistochemistry (Supplementary Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…After MCA occlusion, 2 animals of each age and sex were euthanized and their brains pooled to harvest astrocytes using our previously published procedures (Lewis et al, 2008a, 2008b). This procedure was repeated 3–4 times each time using a new set of animals of each sex and age.…”

Section: Methodsmentioning

confidence: 99%

Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function

Lewis

Thomas

Selvamani

et al. 2012

Neurobiology of Aging

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In middle-aged female rats, focal ischemia leads to a larger cortical infarction as compared with younger females. To determine if stroke-induced cytotoxicity in middle-aged females was associated with impaired astrocyte function, astrocytes were harvested and cultured from the ischemic cortex of young and middle-aged female rats. Middle-aged astrocytes cleared significantly less glutamate from media as compared with young female astrocytes. Furthermore, astrocyte-conditioned media from middle-aged female astrocytes induced greater migration of peripheral blood monocyte cells (PBMCs) and expressed higher levels of the chemoattractant macrophage inflammatory protein-1 (MIP-1). Middle-aged astrocytes also induced greater migration of neural progenitor cells (NPCs), however, their ability to promote neuronal differentiation of neural progenitor cells was similar to young astrocytes. In males, where cortical infarct volume is similar in young and middle-aged animals, no age-related impairment was observed in astrocyte function. These studies show that the aging astrocyte may directly contribute to infarct severity by inefficient glutamate clearance and enhanced cytokine production and suggest a cellular target for improved stroke therapy among older females.

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“…Ex vivo cultures of astrocytes collected from the olfactory bulb of middle-aged female rats show increased stress fiber formation, reduced laminin deposition, increased BDNF expression and reduced TrkB expression compared to young astrocytes (Lewis et al 2008a) and more importantly, aged astrocytes show an impairment in their ability to promote neuronal differentiation of neural progenitor cells (Lewis et al 2008a). Moreover, reduced glutamate uptake has been reported in ex vivo adult, ischemia-activated primary astrocyte cultures collected from 12 mo.…”

Section: The Aging Astrocytementioning

confidence: 99%

Age-related changes in brain support cells: Implications for stroke severity

Sohrabji

Bake

Lewis

2013

Neurochemistry International

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Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells

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Astrocytes from acyclic female rats exhibit lowered capacity for neuronal differentiation

Cited by 8 publications

References 66 publications

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neurotrophic Support in Male and Female Rats

Age Increase of Estrogen Receptor-α (ERα) in Cortical Astrocytes Impairs Neurotrophic Support in Male and Female Rats

Age-related severity of focal ischemia in female rats is associated with impaired astrocyte function

Age-related changes in brain support cells: Implications for stroke severity

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