Selective microglial activation in the rat rotenone model of Parkinson's disease.
Chronic rotenone exposure reproduces features of Parkinson's disease (PD) (Nat. Neurosci. 3 (2000) 1301; Exp. Neurol. 179 (2003) 9). We investigated the role of glial activation in rotenone toxicity in vivo. Male Lewis rats received 2-3 mg/kg rotenone per day for up to 4 weeks. In 50% of surviving rotenone-treated animals, there was nigrostriatal dopaminergic degeneration, marked by reduced tyrosine hydroxylase immunoreactivity). Extensive microglial activation, determined by OX-42-ir, occurred in striatum and nigra of rotenone-treated animals, and was prominent before anatomical evidence of dopaminergic lesions. Microglia enlarged and developed short, stubby processes in rotenone-treated animals. Rotenone-induced microglial activation was less pronounced in cortex. Reactive astrocytosis was minimal and limited to a thin rim around the lesion. Marked microglial activation with minimal astrocytosis is another pathological feature of PD reproduced by rotenone treatment.
Sherer
Todd B
TB
Center for Neurodegenerative Disease, Emory University, 30322, Atlanta, GA, USA.
Betarbet
Ranjita
R
Kim
Jin Ho
JH
Greenamyre
J Timothy
JT
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004781:Environmental Exposure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone / Q000633:toxicity*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D005904:Glial Fibrillary Acidic Protein; D007306:Insecticides; D008562:Membrane Glycoproteins; D012402:Rotenone; D051926:Basigin; D014446:Tyrosine 3-Monooxygenase