Acute treatment with 17β‐estradiol attenuates astrocyte–astrocyte and astrocyte–neuron communication

Abstract

Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control.

Developmental Exposure to Ethinylestradiol Affects Reproductive Physiology, the GnRH Neuroendocrine Network and Behaviors in Female Mouse

“…However, GnRH neurons express low levels of Esr2 gene coding for estrogen receptor β (ERβ) early in development (Skynner et al, 1999 ; Sharifi et al, 2002 ), consistent with a possible direct regulation of EE2 on GnRH neurons. Nonetheless, other mechanisms might occur, such as an indirect effect through the glial microenvironment believed to be a target of estrogenic compounds via ERs and GPR30 during development (McCarthy et al, 2002 ; Merlo et al, 2007 ; Rao and Sikdar, 2007 ) and closely communicating with developing and adult neurons (Kuo et al, 2010 ; Geller et al, 2013 ).…”

The Impact of Neuroimmune Alterations in Autism Spectrum Disorder

“…One important point is that, although the well accepted fact that the CNS undergoes constant immune surveillance that takes place within the meningeal compartment ( 132 ), the real mechanism(s) that guide(s) the entrance and exit of immune cells from the CNS remains to be demonstrated. Recently, an interesting investigation revealed the presence of structures with functional lymphatic vessels lining the dural sinuses, in a place difficult to visualize and actually so far ignored.…”

“…These structures present characteristics of lymphatic endothelial cells and are able to carry both fluid and immune cells from and into the cerebrospinal fluid. Importantly, these structures are connected to the deep cervical lymph nodes ( 132 ). From this view, it is clear that a new and important window of investigation starts, in the search for possible link(s) connecting triggering of ASD to immune system impairment and vice versa .…”

Selective Oestrogen Receptor Modulators Decrease the Inflammatory Response of Glial Cells

“…As shown in Fig. 1, oestradiol regulates the signalling from astrocytes to neurones, which may affect synaptic activity and neuronal excitability (108, 109). By contrast, signalling from neurone to glia also affects the response of glial cells to oestrogenic compounds and neuronal signals regulate the effects of oestradiol on astrocytes (110).…”