title: Ogg1 null mice exhibit age-associated loss of the nigrostriatal pathway and increased sensitivity to MPTP.
abstract: Cumulative damage to cellular macromolecules via oxidative stress is a hallmark of aging and neurodegenerative disease. Whether such damage is a cause or a subsequent effect of neurodegeneration is still unknown. This paper describes the development of an age-associated mild parkinsonian model in mice that lack the DNA repair enzyme 8-oxoguanine glycosylase 1 (Ogg1). Aged OGG1 knock-out (OGG1 KO) mice show a decreased spontaneous locomotor behavior and evidence a decrease in striatal dopamine levels, a loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN), and an increase in ubiquitin-positive inclusions in their remaining SN neurons. In addition, young OGG1 KO mice are more susceptible to the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) than their wild-type (WT) counterparts. Age-associated increases in 7,8-dihydro-2'-deoxyguanine (oxo(8)dG) have been reported in brain regions and neuronal populations affected in Parkinson's disease (PD), toxin-induced parkinsonian models, and mice harboring genetic abnormalities associated with PD. Because of these increased oxo(8)dG levels, the OGG1 KO mouse strain could shed light on molecular events leading to neuronal loss as a consequence of cumulative oxidative damage to DNA during aging and after toxicological challenge.
authors: Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA. Fernando.Cardozo@umontana.edu
authors: Fernando
authors: F
authors: Cardozo-Pelaez
authors: Monica
authors: M
authors: Sanchez-Contreras
authors: Andrew B C
authors: AB
authors: Nevin
mesh_terms: D000375:Aging / Q000187:drug effects / Q000235:genetics* / Q000473:pathology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics; D005260:Female; D020267:MPTP Poisoning / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
chemical_list: D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse