GABA and Neuroactive Steroid Interactions in Glia: New Roles for Old Players?

Abstract

In recent years it has becoming clear that glial cells of the central and peripheral nervous system play a crucial role from the earliest stages of development throughout adult life. Glial cells are important for neuronal plasticity, axonal conduction and synaptic transmission. In this respect, glial cells are able to produce, uptake and metabolize many factors that are essential for neuronal physiology, including classic neurotransmitters and neuroactive steroids. In particular, neuroactive steroids, which are mainly synthesized by glial cells, are able to modulate some neurotransmitter receptors affecting both glia and neurons. Among the signaling systems that are specialized for neuron-glial communication, we can include neurotransmitter GABA.The main focus of this review is to illustrate the cross-talk between neurons and glial cells in terms of GABA neurotransmission and actions of neuroactive steroids. To this purpose, we will review the presence of the different GABA receptors in the glial cells of the central and peripheral nervous system. Then, we will discuss their modulation by some neuroactive steroids.

Deletion of GABA‐B Receptor in Schwann Cells Regulates Remak Bundles and Small Nociceptive C‐fibers

“…By inhibiting the adenylate cyclase and calcium channels or by activating the potassium channels, GABA-B receptors mediate the effects of GABA in the nervous system (Couve et al, 2000;Ulrich and Bettler, 2007). The GABA-B1 isoforms are distributed throughout the neuronal and glial compartments in the brain, in the spinal cord (Charles et al, 2001;Margeta-Mitrovic et al, 1999) and in the dorsal root ganglion (DRG) (Campbell et al, 1993;Charles et al, 2001;Dolphin and Scott, 1986;Magnaghi, 2007;Towers et al, 2000), suggesting the involvement of GABA-B receptors in sensory functions (Bowery, 1993;Fromm, 1989;Hering-Hanit and Gadoth, 2001;Sindrup and Jensen, 2002). The GABA-B1 isoforms are distributed throughout the neuronal and glial compartments in the brain, in the spinal cord (Charles et al, 2001;Margeta-Mitrovic et al, 1999) and in the dorsal root ganglion (DRG) (Campbell et al, 1993;Charles et al, 2001;Dolphin and Scott, 1986;Magnaghi, 2007;Towers et al, 2000), suggesting the involvement of GABA-B receptors in sensory functions (Bowery, 1993;Fromm, 1989;Hering-Hanit and Gadoth, 2001;Sindrup and Jensen, 2002).…”

SKF83959, an Agonist of Phosphatidylinositol-Linked D1-Like Receptors, Promotes ERK1/2 Activation and Cell Migration in Cultured Rat Astrocytes

“…In most cases, the functions of astrocytes are mediated primarily by their membrane transporters and receptors such as the glutamate transporters and classical DA receptors [12], [13], [14]. Putative PI-linked D 1 -like receptors have also been found to modulate astrocyte function.…”

GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone

“…Mammalian species express two isoforms of GAD that differ in their cellular and subcellular distribution, the membrane anchored form of 65 kDa (GAD65) and the cytoplasmic form of 67 kDa (GAD67). Early in the middle 1970s date the first studies on the presence of GABA and its receptors outside the CNS, although their cellular distribution and the physiological significance of their presence have been underestimated mainly in the PNS (see for review Magnaghi 2007; Magnaghi et al. 2009).…”