Role of astroglia in the neuroplastic and neuroprotective actions of estradiol

Abstract

Astrocyte-neuron cross-talk is an essential component of the mechanisms involved in the neuroendocrine and neuroprotective actions of estradiol. Astrocytes express estrogen receptors, show morphological and functional modifications in response to estradiol and participate in the hormonal regulation of synaptic plasticity and neuroendocrine events. In addition, estradiol interferes with the activation of astrocytes under pathological conditions, modulating the release of neurotrophic factors and inflammatory molecules by these cells. Furthermore, under neurodegenerative conditions, astrocytes synthesize estradiol, which acts as a local neuroprotectant. The actions of estradiol on astrocytes can be imitated by selective estrogen receptor modulators. Some of these molecules, which are free of the peripheral risks associated with estrogen therapy, exert estradiol-like anti-inflammatory actions on astrocytes and are potential therapeutic candidates for the control of reactive astrogliosis.

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

“…These cells respond to synaptic transmission and help to regulate and process synaptic information under basal and active conditions (Perea and Araque, 2007;Panatier et al, 2011). Interestingly, estradiol can initiate rapid cellular responses in astrocytes regulating their function (Azcoitia et al, 2010;Micevych et al, 2010), and these cells are capable of synthesizing estradiol (Yague et al, 2006;Azcoitia et al, 2011). However, it is not known what role, if any, astrocytes play in mediating the rapid responses of estrogens, be it as a source of estradiol or by directly contributing to the remodeling of spine morphology/number.…”

“…The contribution of estrogenic regulation of inhibitory neurons and astrocytes in the regulation of dendritic spines has been explored in a number of studies (Murphy et al, 1998;Amateau and McCarthy, 2002;Zhou et al, 2007;Azcoitia et al, 2010;Wojtowicz and Mozrzymas, 2010) but not always in a time frame consistent with that of rapid actions. Previous studies suggested that the ability of estradiol to increase spine density is through a reduction of inhibitory and an increase in excitatory drive in hippocampal neurons (Murphy et al, 1998;Wojtowicz and Mozrzymas, 2010).…”

Depletion of Nrf2 Enhances Inflammation Induced by Oxyhemoglobin in Cultured Mice Astrocytes

“…But there is very few studies focused on the reaction of astrocyte, the most important inflammatory response cell in brain, to SAH. Astrocytes play a critical role in maintaining normal brain physiology and responding to injury or disease [21,22]. After experimental SAH in dog, apoptosis of astrocytes was observed in the hippocampus and cortex [10], which suggests that astrocytes may participate in the reaction to SAH.…”

Injury-Induced Expression of Glial Androgen Receptor in the Zebra Finch Brain

“…[6][7][8][9] This reactive gliosis and subsequent neuronal-glial interactions have both neurodegenerative and neuroprotective effects. [10][11][12] Predominately, this glial response/glial scar forms a physical and molecular barrier to isolate the injured area, and is necessary to re-establish a favorable environment for normal nervous tissue response and repair. 6,9 Specifically, glial cells act on the neurovascular unit, regulate neuroinflammation, and modulate future reactive gliosis.…”