ABSTRACT
The initial identi¡cation of glial cells goes back to the mid-ninetenth century, when the German pathologist Rudolph Virchow indicated the existence in the brain tissue of a nonneuronal component that he described as an interstitial, cement-like substance interposed between the actual nervous elements and holding them together. He called this unusual substance neuroglia and thought it was connective tissue
6.1 Introduction: A Historical Perspective ......................................................... 157 6.2 Astrocytes, Interfaces, and Physiology ......................................................... 158
6.2.1 Territorial Organization and Functions of Protoplasmic Astrocytes ................................................................... 158
6.2.2 Ca2+-Dependent Glutamate Release from Astrocytes ...................... 161 6.3 Reaction of Astrocytes to Injury ................................................................... 163 6.4 Excess Glutamate Release from Astrocytes and Neuronal Cell Death:
The Example of AIDS Dementia Complex .................................................. 164 6.5 Astrocyte Alterations in Alzheimer’s Disease ............................................. 165 6.6 Astrocytes as Players in Amyotrophic Lateral Sclerosis Pathogenesis ........ 167 6.7 Concluding Remarks .................................................................................... 170 Acknowledgments .................................................................................................. 171 References .............................................................................................................. 171
(Virchow 1856). Basic illustrations of what we currently consider astrocytes were made a few years later by Otto Deiters, who depicted stellate cells within the connective tissue reported by Virchow, and represented them with morphological features already distinguishing the ¡brous and protoplasmic cells of white and grey matter (Dieters 1865). It took another 4 years until Jakob Henle and Friedrich Merkel represented a network of star-shaped cells in the white matter of the spinal cord (Henle and Merkel 1869). The next, impressive contribution toward comprehension of the functional roles of astrocytes came, a few years later, from Camillo Golgi and Santiago Ramon y Cajal, thanks to the development of new staining techniques, notably the famous “black reaction.” With this approach, Golgi noted that the processes of astrocytes contact blood vessels and proposed the innovative concept that these cellular elements play a central role in the distribution of energy substratesfrom capillaries to neurons (Golgi 1871). This hypothesis was, however, questioned by Cajal, who believed that the function of glial cells was related to their speci¡c location in the microenvironment of neurons and proposed the isolation theory, according to which astrocytes act as neuronal insulators to avoid incorrect interactions between neurons and to preserve neuronal activity (Cajal 1995). Furthermore, together with his collaborators, Cajal conceived the additional theory that glial cells secrete trophic factors to support neuronal growth (Tello 1911). Although the above concepts have limitations, one needs to acknowledge that the ideas on glial function put forward by Golgi and Cajal are still largely valid nowadays (for a thorough overview see Kettenmann and Ransom 2005). A new impulse to the comprehension of astrocyte physiology came only several decades later, in the 1980s, when electrophysiological recordings with the patch-clamp technique (Neher et al. 1978; Hamill et al. 1981) revealed the presence of voltage-and ligand-gated ion channels in cultured astrocytes (MacVicar 1984; Bevan et al. 1985; Barres et al. 1988, 1990; MacVicar and Tse 1988; Sontheimer et al. 1988) and molecular studies identi¡ed expression of a wide array of neurotransmitter receptors in both cultured and tissue astrocytes, often mirroring the one of neighboring synapses (for review see Verkhratsky et al. 1998). The latter discovery represented an important conceptual breakthrough, as it introduced the idea that astrocytes can sense neuronal activity and be activated by it. In the last two decades this view was extraordinarily expanded, and several new studies have shown that astrocytes can respond to neuronal inputs by releasing a variety of chemical messengers that produce modulatory effects on both neuronal and vascular functions (a process de¡ned as gliotransmission).
