Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators

Acaz‐Fonseca, Estefanía; Sánchez-González, Rebeca; Azcoitia, Íñigo; Arévalo, María Ángeles; Garcia-Segura, Luis Miguel

doi:10.1016/j.mce.2014.01.009

Cited by 85 publications

(50 citation statements)

References 148 publications

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“…Our main focus in this Review is the molecular mechanisms elicited by oestradiol in the brain in vivo, in which the cell types involved have not always been identified. However, it should be noted that glial cells express ERs, including ERα, ERβ and GPER 64,66,67 , and that brain injury induces both the synthesis of oestradiol in reactive astrocytes and the expression of ERs in these cells 68 . This suggests that astrocytes may play an important part in the neuroprotective actions of oestradiol.…”

Section: Normal Conditionsmentioning

confidence: 99%

The neuroprotective actions of oestradiol and oestrogen receptors

2014

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Section: Normal Conditionsmentioning

confidence: 99%

The neuroprotective actions of oestradiol and oestrogen receptors

2014

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“…Several excellent reviews address cell type-specific anti-inflammatory mechanisms of 17βE2 in microglia (Habib and Beyer, 2015; Vegeto et al, 2008), astrocytes (Acaz-Fonseca et al, 2014), endothelial cells (Sohrabji et al, 2013a), and oligodendrocytes (Arevalo et al, 2010) during neurological injury. In young and middle-aged preclinical animal models of stroke, 17βE2 inhibits the activation of the pro-inflammatory transcription factor, nuclear factor-κβ, which induces transcription of numerous cytokines such as tumor necrosis factor-α (TNFα), chemokine ligand 2 (CCL2), interleukin-6 (Vegeto et al, 2008).…”

Section: Mechanisms Of Estrogen Neuroprotectionmentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

165

121

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There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury.

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“…Direct actions have been demonstrated in primary rodent astrocytes cultures where, for instance, estradiol regulates the activation of ERK1/2, PI3K and NF-κB signalling [181, 182]. That astrocytes may be direct targets of estrogenic compounds is also suggested by the finding that they express ERs both in vitro [181, 183-188] and in vivo, in particular after brain injury [14, 128, 151, 164, 189-195]. In addition, there is evidence that estradiol anti-inflammatory and protective effects in experimental autoimmune encephalomyelitis is dependent on the expression of ERα in astrocytes [196-198], indicating that these cells may mediate neuroprotective actions of estrogenic compounds.…”

Section: Neuroprotective Actions Of Estrogenic Compounds After Tbimentioning

confidence: 99%

“…Estrogenic compounds can affect astrocytes, either directly or indirectly, and exert numerous actions in the CNS under physiological and pathological conditions [13]. For instance, it has been shown that estrogenic compounds regulate oedema, extracellular glutamate levels, reactive astrogliosis and inflammatory response after brain trauma [14, 15]. Therefore, they may be useful molecules for the management of TBI [11].…”

Section: Introductionmentioning

confidence: 99%

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

et al. 2018

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Traumatic brain injury (TBI) is a serious public health problem. It may result in severe neurological disabilities and in a variety of cellular metabolic alterations for which available therapeutic strategies are limited. In the last decade, the use of estrogenic compounds, which activate protective mechanisms in astrocytes, has been explored as a potential experimental therapeutic approach. Previous works have suggested estradiol (E2) as a neuroprotective hormone that acts in the brain by binding to estrogen receptors (ERs). Several steroidal and nonsteroidal estrogenic compounds can imitate the effects of estradiol on ERs. These include hormonal estrogens, phytoestrogens and synthetic estrogens, such as selective ER modulators or tibolone. Current evidence of the role of astrocytes in mediating protective actions of estrogenic compounds after TBI is reviewed in this paper. We conclude that the use of estrogenic compounds to modulate astrocytic properties is a promising therapeutic approach for the treatment of TBI.

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Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators

Cited by 85 publications

References 148 publications

The neuroprotective actions of oestradiol and oestrogen receptors

The neuroprotective actions of oestradiol and oestrogen receptors

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

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