Caspase-3 Mediates Apoptosis of Striatal Cells in GA Ⅰ Rat Model

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 32; no. 1; pp. 107 - 112
• Main Author: 田凤艳 付溪 高金枝 张猜 宁琴 罗小平
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.02.2012
• Subjects: aciduria; Amino Acid Metabolism, Inborn Errors - metabolism; Amino Acid Metabolism, Inborn Errors - pathology; Animals; Apoptosis - drug effects; Brain Diseases, Metabolic - metabolism; Brain Diseases, Metabolic - pathology; Caspase 3 - metabolism; Cells, Cultured; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - pathology; Disease Models, Animal; Female; Glutarates; glutaric; Glutaryl-CoA Dehydrogenase - deficiency; Glutaryl-CoA Dehydrogenase - metabolism; I;caspase-;apoptosis;TUNEL; Male; Medicine; Medicine & Public Health; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Rats; Rats, Wistar; type; apoptosis; TUNEL; glutaric aciduria type I; caspase-3
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-012-0019-5

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 evalu-ated 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 bi-lateral striatum by a microscope were observed.TUNEL assay revealed that the apoptotic cells were in-creased 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.