Glial Targets

Astrocytes. Astrocytes constitute about 85% of all glial cells in the CNS thus their numbers surpass all other cell types, including neurons. Occupying this large fraction of total neural mass, it is perhaps not surprising that astrocytes maintain connections with both microvasculature and neurons. This positioning puts them in immediate contact with the incoming source of most neurotoxicants, the blood. Consequently, part of the protective function of astrocytes is their critical role in the formation of the blood-brain barrier (further discussed in Section 31.4.2.2). Astrocyte endfeet (the widened ends of astrocyte projections) wrap around capillaries and encapsulate 

Oligodendrocytes are extremely sensitive to insults that promote oxidative stress, such as inflammation and excessive glutamate signaling. Oligodendrocyte precursors are particularly susceptible to developmental exposure to lead at low doses. 

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Schwarcz R, Pellicciari R (2002) Manipulation of brain kynurenines glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther 303 1-10... 

Garcia, S.J., F.J. Seidler, T.L. Crumpton and T.A. Slotkin. Does the developmental neurotoxicity of chlorpyrifos involve glial targets Macromolecule synthesis, adenylyl cyclase signaling, nuclear transcription factors, and formation of reactive oxygen in C6 glioma cells. Brain Res. 891 54-68, 2001. 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Oshio, K., Binder, D. K., Bollen, A., Verkman, A. S., Berger, M. S. and Manley, G. T. Aquaporin-1 expression in human glial tumors suggests a potential novel therapeutic target for tumor-associated edema. Acta Neurochir. 86(Suppl.) 499-502, 2003. 

Cell adhesion molecules (CAMs) play critical roles in all facets of nervous system development and maintenance. Important phenomena in which CAMs are involved include initial formation of the neural tube and the neural crest, migration of all neurons and glial cells, axonal outgrowth and guidance, target selection, synaptic stabilization and plasticity, myelination and nerve regeneration after injury (see Chs 4,24,28-30 and 53). Adhesion molecules interact with each other and with nonadhesive cell-surface and/or cytoplasmic molecules, and, in the two... 

The glial-derived neurotrophic factor family represents a newly recognized family of target-derived neurotrophic factors 480... 

Neuregulins are likely to act principally in a paracrine manner on adjacent glial cells and on non-neuronal targets tissues innervated by neuregulin-expressing neurons (such as muscle). 

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