TAILIEUCHUNG - Role of astrocytes in manganese mediated neurotoxicity

Astrocytes are responsible for numerous aspects of metabolic support, nutrition, control of the ion and neurotransmitter environment in central nervous system (CNS). Failure by astrocytes to support essential neuronal metabolic requirements plays a fundamental role in the pathogenesis of brain injury and the ensuing neuronal death. | Sidoryk-Wegrzynowicz and Aschner BMC Pharmacology and Toxicology 2013 14 23 http 2050-6511 14 23 BMC Pharmacology Toxicology REVIEW Open Access Role of astrocytes in manganese mediated neurotoxicity Marta Sidoryk-Wegrzynowicz1 and Michael Aschner1 2 Abstract Astrocytes are responsible for numerous aspects of metabolic support nutrition control of the ion and neurotransmitter environment in central nervous system CNS . Failure by astrocytes to support essential neuronal metabolic requirements plays a fundamental role in the pathogenesis of brain injury and the ensuing neuronal death. Astrocyte-neuron interactions play a central role in brain homeostasis in particular via neurotransmitter recycling functions. Disruption of the glutamine Gln glutamate Glu -y-aminobutyric acid GABA cycle GGC between astrocytes and neurons contributes to changes in Glu-ergic and or GABA-ergic transmission and is associated with several neuropathological conditions including manganese Mn toxicity. In this review we discuss recent advances in support of the important roles for astrocytes in normal as well as neuropathological conditions primarily those caused by exposure to Mn. Keywords Astrocytes Manganese Mn Neurodegeneration Transporter Glutamine Gln Glutamate Glu Neurotransmission PKC signaling Ubiquitin-mediated proteolytic system Manganese general characteristics and toxicity Mn is an essential trace metal which is commonly found in the environment. Mn is present in all tissues and is required for the maintenance of proper function and regulation of numerous biochemical cellular reactions 1 . Mn is an integral component of multiple enzymes including glutamine synthetase GS mitochondrial superoxide dismutase SOD arginase and pyruvate carboxylae 2 . On the other hand in humans excess deposition of Mn in the central nervous system CNS leads to neurological abnormalities referred to as manganism 3 . Manganism is characterized by variety of psychiatric cognitive and

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