Document Detail


Manganese neurotoxicity and glutamate-GABA interaction.
MedLine Citation:
PMID:  12742094     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brain extracellular concentrations of amino acids (e.g. aspartate, glutamate, taurine) and divalent metals (e.g. zinc, copper, manganese) are primarily regulated by astrocytes. Adequate glutamate homeostasis is essential for the normal functioning of the central nervous system (CNS). Glutamate is of central importance for nitrogen metabolism and, along with aspartate, is the primary mediator of the excitatory pathways in the brain. Similarly, the maintenance of proper manganese levels is important for normal brain functioning. Several in vivo and in vitro studies have linked increased manganese concentrations with alterations in the content and metabolism of neurotransmitters, namely dopamine, gamma-aminobutyric acid, and glutamate. It has been reported by our laboratory and others, that cultured rat primary astrocytes exposed to manganese displayed decreased glutamate uptake, thereby increasing the excitotoxic potential of glutamate. Furthermore, decreased uptake of glutamate has been associated with decreased gene expression of glutamate:aspartate transporter (GLAST) in manganese-exposed astroctyes. Additional studies have suggested that attenuation of astrocytic glutamate uptake by manganese may be a consequence of reactive oxygen species (ROS) generation. Collectively, these data suggest that excitotoxicity may occur due to manganese-induced altered glutamate metabolism, representing a proximate mechanism for manganese-induced neurotoxicity.
Authors:
Keith M Erikson; Michael Aschner
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Neurochemistry international     Volume:  43     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:    2003 Sep-Oct
Date Detail:
Created Date:  2003-05-13     Completed Date:  2003-08-19     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  475-80     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA. kerikson@wfubmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Glutamic Acid / metabolism*
Humans
Manganese / pharmacology*
gamma-Aminobutyric Acid / metabolism*
Chemical
Reg. No./Substance:
56-12-2/gamma-Aminobutyric Acid; 56-86-0/Glutamic Acid; 7439-96-5/Manganese

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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