Kim, JH Kim, S Yoon, IS Lee, JH Jang, BJ Jeong, SM Lee, JH Lee, BH Han, JS Oh, S Kim, HC Park, TK Rhim, H Nah, SY 2024-01-21T05:10:40Z 2024-01-21T05:10:40Z 2021-09-03 2005-04 0028-3908 https://pubs.kist.re.kr/handle/201004/136593 The precise cause of neuronal cell death in Huntington's disease (HD) is not known. Systemic administration of 3-nitropropionic acid (3-NP), an irreversible succinate dehydrogenase inhibitor, not only induces a cellular ATP depletions but also causes a selective striatal degeneration similar to that seen in HD. Recent accumulating reports have shown that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, we examined in vitro and in vivo effects of GTS on striatal neurotoxicity induced by repeated treatment of 3-NP in rats. Here, we report that systemic administration of GTS produced significant protections against systemic 3-NP- and intrastriatal malonate-induced lesions in rat striatum with dose-dependent manner. GTS also improved significantly 3-NP-caused behavioral impairment and extended survival. However, GTS itself had no effect on 3-NP-induced inhibition of succinate dehydrogenase activity. To explain the mechanisms underlying in vivo protective effects of GTS against 3-NP-induced striatal degeneration, we examined in vitro effect of GTS against 3-NP-caused cytotoxicity using cultured rat striatal neurons. We found that GTS inhibited 3-NP-induced intracellular Ca2+ elevations. GTS restored 3-NP-caused mitochondrial transmembrane potential reduction in cultured rat striatal neurons. GTS also prevented 3-NP-induced striatal neuronal cell deaths with dose-dependent manner. The EC50 was 12.6 +/- 0.7 mu g/ml. These results suggest that in vivo protective effects of GTS against 3-NP-induced rat striatal degeneration might be achieved via in vitro inhibition of 3-NP-induced intracellular Ca2+ elevations and cytotoxicity of striatal neurons. (c) 2005 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD MITOCHONDRIAL TOXIN SUCCINATE-DEHYDROGENASE HUNTINGTONS-DISEASE GINSENOSIDES RB1 CA2+ CHANNELS IN-VIVO NEURONS MECHANISMS GLUTAMATE RECEPTOR Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats Article 10.1016/j.neuropharm.2004.12.013 1 NEUROPHARMACOLOGY, v.48, no.5, pp.743 - 756 NEUROPHARMACOLOGY 48 5 743 756 scie scopus 000228707900012 2-s2.0-20144389219 Neurosciences Pharmacology & Pharmacy Neurosciences & Neurology Pharmacology & Pharmacy Article MITOCHONDRIAL TOXIN SUCCINATE-DEHYDROGENASE HUNTINGTONS-DISEASE GINSENOSIDES RB1 CA2+ CHANNELS IN-VIVO NEURONS MECHANISMS GLUTAMATE RECEPTOR ginseng saponins 3-nitropropionic acid striatum toxicity neuroprotection