Alpha-synuclein deficient mice are resistant to toxin-induced multiple system atrophy.
Multiple systems atrophy (MSA) is a neurodegenerative disorder characterized by oligodendrocytic accumulations of alpha-synuclein (alphasyn). Oxidative stress is a key mechanism proposed to underlie MSA pathology. To address the role of alphasyn modifications, over and above general oxidative modifications, this study examined the effects of 3-nitropropionic acid (3NP) administration, a technique used to model MSA, in knock-out mice lacking alphasyn (alphasynKO). Although susceptible to 3NP-induced oxidative stress, alphasynKO mice display reduced neuronal loss and dendritic pathology. The alphasynKO mice are resistant to 3NP-induced motor deficits and display attenuated loss of tyrosine hydroxylase and dopamine transporter striatal immunoreactivity. The results suggest that deficits in MSA are not due to general oxidative protein modification but in addition may be related to specific alphasyn modifications.
Ubhi
Kiren
K
Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, California 92093-0624, USA.
Rockenstein
Edward
E
Mante
Michael
M
Inglis
Chandra
C
Adame
Anthony
A
Patrick
Christina
C
Masliah
Eliezer
E
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019578:Multiple System Atrophy / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009574:Nitro Compounds / Q000008:administration & dosage / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics* / Q000502:physiology
D009574:Nitro Compounds; D011422:Propionates; D051844:alpha-Synuclein; C015392:3-nitropropionic acid