Astrocytes: Wiring the Brain PDF

Preface: The Astrocyte: A Polarized Cell

The goal of this book has been to compile an overview of the most current findings on the diverse roles played by astrocytes in central nervous system (CNS) function and dysfunction, emphasizing how the connections that the astrocyte makes with other cells of the brain are essential for a variety of important neural functions. A key concept that we have highlighted throughout (wiring the brain) is that astrocytes are morphologically highly elaborated cells, establishing associations through their fine processes with practically all cellular types in the CNS. Such close morphological associations, together with the fact that astrocytes express a multitude of ion channels, transporters, and membrane receptors, endow these cells with the unique capability to sense and influence diverse CNS functions.

A view of the astrocyte that is now becoming classical is that one or more of its processes surrounds synaptic areas of neurons (providing the third element of the so-called tripartite synapse) and another process projecting toward the vasculature to provide a bidirectional pathway for nutrient delivery from the blood supply and metabolite clearance toward the vasculature. Moreover, astrocytes are highly polarized, being specialized for interactions with each neural cell type. In contrast to cell polarity present in epithelial cells, where basolateral and apical domains are separated by junctions with fence and barrier properties, the polarity of astrocytes is similar to interneurons, where distinct processes mediate input and output functions and possess the proteins specifying either pre- or postsynaptic functions. Like neurons, astrocytes integrate information and are believed able to relay it through intracellular calcium wave signaling.

We have divided this book into three sections, with the individual sections dealing with biomarkers that define astrocytes, connections of astrocytes to other neural cells, and damage to astrocytes in disease. Specifically, chapters in Section I identify major astrocyte biomarkers and how they define the different connectivity domains. Chapters in Section II describe the role of these connections, how their function can be manipulated under physiological conditions, and how dysfunction of the connectivity leads to aberrant brain performance. Chapters in Section III examine the alterations of glia that have been observed in specific diseases of the brain (epilepsy, autoimmune encephalitis (MS), Alzheimer's, autism, and major depression) and attempts to identify key mechanisms responsible for these alterations.

As research becomes more and more translational, we expect that compilations such as this will be increasingly useful in defining both the state of what is known with regard to a specific field and what is unknown with regard to causes of pathological conditions and the possibility for novel therapeutic strategies.