title: Role of transcription factor yin yang 1 in manganese-induced reduction of astrocytic glutamate transporters: Putative mechanism for manganese-induced neurotoxicity.
abstract: Astrocytes are the most abundant non-neuronal glial cells in the brain. Once relegated to a mere supportive role for neurons, contemporary dogmas ascribe multiple active roles for these cells in central nervous system (CNS) function, including maintenance of optimal glutamate levels in synapses. Regulation of glutamate levels in the synaptic cleft is crucial for preventing excitotoxic neuronal injury. Glutamate levels are regulated predominantly by two astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST). Indeed, the dysregulation of these transporters has been linked to several neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD), as well as manganism, which is caused by overexposure to the trace metal, manganese (Mn). Although Mn is an essential trace element, its excessive accumulation in the brain as a result of chronic occupational or environmental exposures induces a neurological disorder referred to as manganism, which shares common pathological features with Parkinsonism. Mn decreases the expression and function of both GLAST and GLT-1. Astrocytes are commonly targeted by Mn, and thus reduction in astrocytic glutamate transporter function represents a critical mechanism of Mn-induced neurotoxicity. In this review, we will discuss the role of astrocytic glutamate transporters in neurodegenerative diseases and Mn-induced neurotoxicity.
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, United States.
authors.forename: Pratap
authors.initials: P
authors.lastname: Karki
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, United States.
authors.forename: Keisha
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, United States.
authors.forename: James
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, TN 37208, United States. Electronic address: elee@mmc.edu.
authors.forename: Eunsook
authors.initials: E
authors.lastname: Lee
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D020149:Manganese Poisoning / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D050986:YY1 Transcription Factor / Q000502:physiology*
chemical_list: D027322:Amino Acid Transport System X-AG; D014157:Transcription Factors; D050986:YY1 Transcription Factor; D008345:Manganese
keywords: Astrocytes; GLAST; GLT-1; Glutamate; Manganese; Neurotoxicity