Review : Glial Neuronal Interactions: A Physiological Perspective

Abstract

Throughout the nervous system, neurons are closely surrounded by glial cells, leaving only a 20-nm wide extracellular space filled with interstitial fluid. Ions, transmitters, hormones, nutrients, and waste products all share this narrow diffusion pathway. Because the interstitial space occupies only a small volume, neuronal activity can lead to appreciable changes in the extracellular concentration of ions, protons, and neurotransmitters. These changes can affect neuronal activity and are believed to be influenced by glial cells. The proximity of glial processes to synapses and axons make glial cells ideal partners to sequester ions and transmitters released by neurons. The failure of glial cells to perform such essential homeostatic functions can have profound effects, and these homeostatic activities may constitute one way in which glial cells can influence neuronal signaling. In addition, glial cells, which, unlike most neurons, are coupled to each other through gap-junctions, communicate with each other and possibly also with adjacent neurons through propagated intracellular Ca 2+ waves. The importance of such interglial signaling is not understood. Additionally, glial cells and neurons mutually modulate their expression of ion channels, most likely through factors released into the extracellular space. The range of responses observed in glial cells and their intimate anatomical relationship with neurons suggest a broader role for glia than is currently appreciated. It also emphasizes the importance of a better understanding of glial-neuronal interactions to an understanding of brain function. The Neuroscientist 1: [328][329][330][331][332][333][334][335][336][337] 1995

Role and Mechanisms of Interleukin-1 in the Modulation of Neurotoxicity

“…One likely explanation for this find- ing was that neurons in vivo may be protected against prolonged glutamate exposure by the powerful presynaptic neuronal and glial glutamate uptake system, particularly the uptake system of astrocytes [27,33,51]. Astrocytes are thought to play a critical role in the protection of neurons against NMDA receptor-mediated injury [52]. In this context, glutamine synthetase, which is found predominantly in astrocytes, metabolizes glutamate into glutamine.…”

“…Results of studies of microglial activation by cytokines have included the following: (1) proliferation [14,38]; (2) transformation into phagocytic cells with macrophage morphology [18,52]; (3) upregulation of cell surface molecules [56] and (4) release of secretory products [1,3,4,6,8,37,41], such as cytokines and neurotrophins. The results of our studies included activation of microglia after a combined treatment of LPS plus IFN-Á in cocultures with neurons that was clearly neurotoxic.…”

Ras Family GTPases Control Growth of Astrocyte Processes

“…Their processes serve as tracts for migrating neuroblasts (Cameron and Rakic, 1991), and contact nodes of Ranvier and ensheathe synapses where they buffer potassium ions and neurotransmitters (Ffrench-Constant et al, 1986;Mennerick and Zorumski, 1994;Hansson and Ronnback, 1995;Sontheimer, 1995;Mennerick et al, 1996). When astrocytes are removed from the brain into cell culture in the absence of neurons, they fail to extend their processes and instead divide and grow as a flat fibroblast-like contact-inhibited monolayer (Hatten, 1985).…”

Electrophysiological Changes That Accompany Reactive GliosisIn Vitro

“…Underlying mechanisms are not well understood, but studies suggest that intracellular pH (Pappas et al, 1994) or intracellular Na ϩ (Knutson et al, 1997) are critically important. Moreover, involvement of ion channel activity in cell cycle control has been documented for other inexcitable cells (for review, see Sontheimer, 1995).…”