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Astrocyte Dysfunctions and HIV-1 Neurotoxicity
1Neurophysiology Laboratory, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Abstract:
Astrocytes play an important role in maintaining an optically suited milieu for neuronal functionality, and are involved in the progression and outcome of many neuropathological conditions. It becomes increasingly evident that astrocytes are significant contributors to HIV-1 associated neurological disorders by modulating the microenvironment in the central nervous system and releasing proinflammatory cytokines. Recent studies have revealed direct metabolic interactions between neurons and astrocytes observed particularly in HIV-1-associated neurological disorders by which astrocytic dysfunctions disregulate extracellular K+ homeostasis, intracellular calcium concentration, glutamate clearance, and blood brain barrier integrity and permeability. Such dysfunctions are amplified via gap junctions, directly or indirectly impacting surrounding neurons and significantly contributing to the pathogenesis of HIV-1-associated neuropathology. In this review, we tentatively address recent progresses on the roles astrocytes may play in HIV-1-associated neurotoxicity.
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