Mitochondrial NAD+-linked State 3 respiration and complex-I activity are compromised in the cerebral cortex of 3-nitropropionic acid-induced rat model of Huntington's disease |
| |
Authors: | Pandey Mritunjay Varghese Merina Sindhu Kizhakke M Sreetama Sen Navneet A K Mohanakumar Kochupurackal P Usha Rajamma |
| |
Affiliation: | Laboratory of Clinical &Experimental Neuroscience, Division of Cell Biology &Physiology, Indian Institute of Chemical Biology, Kolkata, India; Manovikas Biomedical Research and Diagnostic Centre, Kolkata, India |
| |
Abstract: | Mitochondrial complex-I dysfunction has been observed in patients of Huntington's disease (HD). We assessed whether such a defect is present in the 3-nitropropionic acid (3-NP) model of HD. Rats treated with 3-NP (10–20 mg/kg i.p., for 4 days) exhibited weight loss, gait abnormalities, and striatal lesions with increased glial fibrillary acidic protein immunostaining on fifth and ninth days, while increase in striatal dopamine and loss of tyrosine hydroxylase immunoreactivity were observed on fifth day following treatment. We report for the first time a dose-dependent reduction in complex-I activity in the cerebral cortex when analyzed spectrophotometrically and by blue native-polyacrylamide gel electrophoresis following 3-NP treatment. The citrate synthase normalized activities of mitochondrial complex-I, -II, -(I + III) and -IV were decreased in the cortex of 3-NP treated rats. In addition, succinate driven State 3 respiration was also significantly inhibited in vivo and in the isolated mitochondria. These findings taken together with the observation of a significant decrease in vivo but not in vitro of State 3 respiration with NAD+-linked substrates, suggest complex-I dysfunction in addition to irreversible inhibition of complex-II and succinate dehydrogenase activity as a contributing factor in 3-NP-induced cortico-striatal lesion. |
| |
Keywords: | BN-PAGE cortico-striatal neurodegeneration electron transport chain footprint analysis GFAP striatal dopamine succinate dehydrogenase |
本文献已被 PubMed 等数据库收录! |
|