title: Caspase-3 mediates apoptosis of striatal cells in GA I rat model.
abstract: In previous study, glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro. In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism, 34 male pups were randomly assigned to NS group, low dose GA (LGA, 5 μmol GA/g body weight) group and high dose GA (HGA, 10 μmol GA/g body weight) group. These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am, 15:00 pm and 22:30 pm and killed 12 h after the last injection. Microscopic pathology in corpus striatum was evaluated by HE staining. The apoptotic cells were identified by TUNEL staining. The transcript levels of caspase-3, 8, 9, Bax, Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting. In LGA and HGA groups, ventricle collapse, cortical atrophy by a macroscope and interstitial edema, vacuolations, widened perivascular space of bilateral striatum by a microscope were observed. TUNEL assay revealed that the apoptotic cells were increased in LGA and HGA groups. The transcript of caspase-3 was up-regulated to 2.5 fold, accompanied by the up-regulation of caspase-9, Bax and down-regulation of Bcl-2. The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups. The rat model for GA I showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion. Further studies should be taken to investigate the underlying mechanisms.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. xpluo@tjh.tjmu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Luo
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001928:Brain Diseases, Metabolic / Q000378:metabolism* / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005977:Glutarates; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005977:Glutarates; D050770:Glutaryl-CoA Dehydrogenase; D053148:Caspase 3; C035736:glutaric acid