Manganese toxicity in the central nervous system: The glutamine/glutamate-γ-aminobutyric acid cycle

M. Sidoryk-Wegrzynowicz, Michael Aschner

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Manganese (Mn) is an essential trace element that is required for maintaining proper function and regulation of numerous biochemical and cellular reactions. Despite its essentiality, at excessive levels Mn is toxic to the central nervous system (CNS). Increased accumulation of Mn in specific brain regions, such as the substantia nigra, globus pallidus and striatum, triggers neurotoxicity resulting in a neurological brain disorder, termed manganism. Mn has been also implicated in the pathophysiology of several other neurodegenerative diseases. Its toxicity is associated with disruption of the glutamine (Gln)/glutamate (Glu)-γ-aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons, thus leading to changes in Glu-ergic and/or GABAergic transmission and Gln metabolism. Here we discuss the common mechanisms underlying Mn-induced neurotoxicity and their relationship to CNS pathology and GGC impairment.

Original languageEnglish (US)
Pages (from-to)466-477
Number of pages12
JournalJournal of Internal Medicine
Volume273
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Aminobutyrates
Manganese
Glutamine
Glutamic Acid
Central Nervous System
Globus Pallidus
Poisons
Trace Elements
Brain Diseases
Substantia Nigra
Nervous System Diseases
Astrocytes
Neurodegenerative Diseases
Pathology
Neurons
Brain

Keywords

  • γ-aminobutyric acid (GABA)
  • Astrocytes
  • Glutamate (Glu)
  • Glutamine (Gln)
  • Manganese
  • Neurotransmission

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Manganese toxicity in the central nervous system : The glutamine/glutamate-γ-aminobutyric acid cycle. / Sidoryk-Wegrzynowicz, M.; Aschner, Michael.

In: Journal of Internal Medicine, Vol. 273, No. 5, 05.2013, p. 466-477.

Research output: Contribution to journalArticle

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