Estrogen as a Neuroprotectant in Both Sexes: Stories From the Bird Brain

Saldanha, Colin J.

doi:10.3389/fneur.2020.00497

Cited by 17 publications

(11 citation statements)

References 90 publications

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“…Recent investigations have revealed pronounced interactions of estrogens with the dopaminergic system, a highly implicated system in the pathophysiology of multiple psychiatric and neurodegenerative disorders, and that they modulate executive functions, such as working memory and reward processing [ 6 , 7 , 8 ]. Further, the roles of estrogen receptors and estrogen signaling have been highlighted, with studies reporting their neuroprotective effects on the brain by promoting neurotrophins synthesis and protecting the brain from inflammation and stress [ 9 , 10 , 11 ]. To add more, investigations revealed, in animal models of psychiatric disorders and in patients, that estrogen and estrogen signaling are disturbed and that they are associated with not only the cognitive deficits but, also, the manifestations of the symptoms, which could also be reversed with estrogen administration or treatments targeting estrogen-signaling pathways [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

Hwang

Lee

Kim

et al. 2020

IJMS

112

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Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

Hwang

Lee

Kim

et al. 2020

IJMS

112

View full text Add to dashboard Cite

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“…In this study, the direct involvement of the mitochondrial estrogen receptor beta (mtERβ) in the activation of the mitochondrial defense antioxidant and anti-apoptotic activities is demonstrated. Accumulated evidence substantiates the regulatory and protective actions of estrogens on the brain, affecting both glial and neuronal physiology [ 17 , 21 , 32 , 33 , 34 , 35 ]. Particularly, the regulation of neuronal mitochondrial functions by estrogen is widely accepted [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 98%

“…Thus, estrogen is proposed to promote neuronal survival, to control neuronal excitability and synaptic plasticity, and to regulate neuronal differentiation, brain development, neuronal homeostasis, and astroglial and microglial inflammatory responses [ 19 , 20 ]. Both nuclear and membrane estrogen receptors participate in estradiol neuroprotective actions, among others, via the control of aromatase, b-cell lymphoma 2 (BCL-2) family member and cytokine synthesis, glycogen synthase kinase-3β (GSK3β) inhibition, glutamate uptake, and calcium and ROS level regulation [ 19 , 20 , 21 ]. ERs actions also involve interactions with alternative pathways orchestrated by other neuroprotective factors, namely insulin growth factor-1, brain derived neurotrophic growth factor, and regulatory factors of WNT (Wingless-Int) and Notch signaling [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Apoptotic and Antioxidant Activities of the Mitochondrial Estrogen Receptor Beta in N2A Neuroblastoma Cells

Tsialtas

Georgantopoulos

Karipidou

et al. 2021

IJMS

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Estrogens are steroid hormones that play a crucial role in the regulation of the reproductive and non-reproductive system physiology. Among non-reproductive systems, the nervous system is mainly affected by estrogens due to their antioxidant, anti-apoptotic, and anti-inflammatory activities, which are mediated by membranous and nuclear estrogen receptors, and also by non-estrogen receptor-associated estrogen actions. Neuronal viability and functionality are also associated with the maintenance of mitochondrial functions. Recently, the localization of estrogen receptors, especially estrogen receptor beta, in the mitochondria of many types of neuronal cells is documented, indicating the direct involvement of the mitochondrial estrogen receptor beta (mtERβ) in the maintenance of neuronal physiology. In this study, cell lines of N2A cells stably overexpressing a mitochondrial-targeted estrogen receptor beta were generated and further analyzed to study the direct involvement of mtERβ in estrogen neuroprotective antioxidant and anti-apoptotic actions. Results from this study revealed that the presence of estrogen receptor beta in mitochondria render N2A cells more resistant to staurosporine- and H2O2-induced apoptotic stimuli, as indicated by the reduced activation of caspase-9 and -3, the increased cell viability, the increased ATP production, and the increased resistance to mitochondrial impairment in the presence or absence of 17-β estradiol (E2). Thus, the direct involvement of mtERβ in antioxidant and anti-apoptotic activities is documented, rendering mtERβ a promising therapeutic target for mitochondrial dysfunction-associated degenerative diseases.

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“…A similar increase in aromatase expression in reactive astrocytes has been detected after traumatic brain injury, where aromatase is induced by inflammatory signals and is neuroprotective by the local generation of estradiol. 15 , 104 This suggests that central aromatase induction may be a general neuroprotective mechanism activated after an acute brain injury. Unfortunately, there is no information on whether aromatase expression is modified in the human brain after traumatic injury or stroke.…”

Section: Brain Aromatase Under Pathological Conditionsmentioning

confidence: 99%

Aromatase in the Human Brain

Azcoitia

Méndez

Garcia-Segura

2021

Androgens: Clinical Research and Therapeutics

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The aromatase cytochrome P450 (P450arom) enzyme, or estrogen synthase, which is coded by the CYP19A1 gene, is widely expressed in a subpopulation of excitatory and inhibitory neurons, astrocytes, and other cell types in the human brain. Experimental studies in laboratory animals indicate a prominent role of brain aromatization of androgens to estrogens in regulating different brain functions. However, the consequences of aromatase expression in the human brain remain poorly understood. Here, we summarize the current knowledge about aromatase expression in the human brain, abundant in the thalamus, amygdala, hypothalamus, cortex, and hippocampus and discuss its role in the regulation of sensory integration, body homeostasis, social behavior, cognition, language, and integrative functions. Since brain aromatase is affected by neurodegenerative conditions and may participate in sex-specific manifestations of autism spectrum disorders, major depressive disorder, multiple sclerosis, stroke, and Alzheimer's disease, we discuss future avenues for research and potential clinical and therapeutic implications of the expression of aromatase in the human brain.

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Estrogen as a Neuroprotectant in Both Sexes: Stories From the Bird Brain

Cited by 17 publications

References 90 publications

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders

Anti-Apoptotic and Antioxidant Activities of the Mitochondrial Estrogen Receptor Beta in N2A Neuroblastoma Cells

Aromatase in the Human Brain

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