title: Differential caspase activity in the cortex and striatum with chronic infusion of 3-nitropropionic acid.
abstract: Systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of select striatal lesions, and some reports provide clues about this pathology. In this study, we investigated the relationship between reduced levels of brain-derived neurotrophic factor (BDNF) in lesioned brain regions and caspase activity, as well as involvement of apoptosis signal-regulating kinase 1 (ASK1) in caspase activation. We analyzed apoptotic cell death, BDNF distribution, caspase-3 activity, caspase-6 activity, ASK1 expression level, and active ASK1 in the cortex and striatum. There were different levels and distributions of these factors within each sub-region. Caspase-6 activity was reduced with down-regulation of ASK1 in the cortex. BDNF protein levels did not decrease in the cortex, but there was replenishment of severely reduced BDNF in the striatum. The present study suggests that an increase in ASK1 in the damaged cortex is related to caspase-6 activation and is involved in cortical depletion of BDNF in the striatum. Furthermore, with systemic infusion of 3-NP, differential expression of ASK1 in the cortex and striatum suggests that this kinase may modulate caspase activation and striatal degeneration.
authors: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea.
authors: Kyoung Joo
authors: KJ
authors: Cho
authors: Department of Neurology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seoul, South Korea. Electronic address: gyungkim@yuhs.ac.
authors: Gyung Whan
authors: GW
authors: Kim
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D057967:Infusions, Intraventricular; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009574:Nitro Compounds / Q000008:administration & dosage*; D011422:Propionates / Q000008:administration & dosage*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009574:Nitro Compounds; D011422:Propionates; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse; D020169:Caspases; C015392:3-nitropropionic acid
keywords: 3-Nitropropionic acid; Apoptosis signal-regulating kinase 1; Caspase-3; Caspase-6; siRNA