title: Glial reactivity in resistance to methamphetamine-induced neurotoxicity.
abstract: Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resistance has not been examined. Thus, this study examined glial-fibrillary acidic protein (GFAP) and CD11b protein expression in striata of animals administered saline or a neurotoxic regimen of METH on post-natal days 60 and/or 90 (Saline:Saline, Saline:METH, METH:Saline, METH:METH). Consistent with previous work, animals experiencing acute toxicity (Saline:METH) showed both activated microglia and astocytes, whereas those resistant to the acute toxicity (METH:METH) did not show activated microglia. Interestingly, GFAP expression remained elevated in rats exposed to METH at PND60 (METH:Saline), and was not elevated further in resistant rats treated for the second time with METH (METH:METH). These data suggest that astrocytes remain reactive up to 30 days post-METH exposure. In addition, these data indicate that astrocyte reactivity does not reflect acute, METH-induced DA terminal toxicity, whereas microglial reactivity does.
authors: Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, Utah, USA.
authors: Danielle M
authors: DM
authors: Friend
authors: Kristen A
authors: KA
authors: Keefe
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D039481:CD11b Antigen / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D005334:Fever / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D039481:CD11b Antigen; D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D008694:Methamphetamine; D004298:Dopamine