Purinergic trophic signalling in glial cells: functional effects and modulation of cell proliferation, differentiation, and death

Abstract

In the last decades, the discovery that glial cells do not only fill in the empty space among neurons or furnish them with trophic support but are rather essential participants to the various activities of the central and peripheral nervous system has fostered the search for the signalling pathways controlling their functions. Since the early 1990s, purines were foreseen as some of the most promising candidate molecules. Originally just a hypothesis, this has become a certainty as experimental evidence accumulated over years, as demonstrated by the exponentially growing number of articles related to the role of extracellular nucleotides and nucleosides in controlling glial cell functions. Indeed, as new functions for already known glial cells (for example, the ability of parenchymal astrocytes to behave as stem cells) or new subtypes of glial cells (for example, NG2 + cells, also called polydendrocytes) are discovered also, new actions and new targets for the purinergic system are identified. Thus, glial purinergic receptors have emerged as new possible pharmacological targets for various acute and chronic pathologies, such as stroke, traumatic brain and spinal cord injury, demyelinating diseases, trigeminal pain and migraine, and retinopathies. In this article, we will summarize the most important and promising actions mediated by extracellular purines and pyrimidines in controlling the functions, survival, and differentiation of the various "classical" types of glial cells (i.e., astrocytes, oligodendrocytes, microglial cells, Müller cells, satellite glial cells, and enteric glial cells) but also of some rather new members of the family (e.g., polydendrocytes) and of other cells somehow related to glial cells (e.g., pericytes and spinal cord ependymal cells).

Differentiation of adipose-derived stem cells into Schwann cell phenotype induces expression of P2X receptors that control cell death

“…Transient ATP stimulation opens the P2X 7 channel to small cations (that is, Na + , K + and Ca 2+ ), whereas a continued exposure to ATP triggers the formation of larger transmembrane pores, determining excessive Ca 2+ influx with consequent changes in intracellular ions and metabolites concentrations, leading to cell death. 49, 50 …”

Inflammation, oxidative stress, and glial cell activation characterize stellate ganglia from humans with electrical storm

“…Several lines of evidence suggest that SGCs have bidirectional interactions with the neurons that they surround and with preganglionic nerve terminals. SGCs express ion channels (29), which provide a mechanism for regulation of the extracellular fluid composition, receptors for neurotransmitters (30) and neurotrophic factors (31), and they are able to release mediators that affect neurons (23). Furthermore, active control of the neuronal microenvironment by SGCs can contribute to disease (32).…”

The purinergic neurotransmitter revisited: A single substance or multiple players?

“…For example, activation of P2X7 receptors on medullary and spinal cord neurons facilitated glutamate release (Deuchars et al, 2001; Deng & Fyffe, 2004; see Sperlagh et al, 2006). Functional P2X1/P2X5, P2X7, P2Y1, P2Y2 as well as all subtypes of adenosine P1 receptors are expressed on CNS astrocytes and other glia cell types (Brodie et al, 1998; Biber et al, 1999; Fam et al, 2000; Fumagalli et al, 2003; Trincavelli et al, 2004; Wittendorp et al, 2004; Lalo et al, 2008; Nagasawa et al, 2009; Verkhratsky et al, 2009; Abbracchio et al, 2009; Lecca et al, 2012). Thus there is diverse expression of purinergic receptors on neurons and glial cells in the CNS that could regulate a wide range of responses to extracellular purines.…”