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Titolo:
Neurotoxicity of the organochlorine insecticide heptachlor to murine striatal dopaminergic pathways
Autore:
Kirby, ML; Barlow, RL; Bloomquist, JR;
Indirizzi:
Virginia Polytech Inst & State Univ, Dept Entomol, Neurotoxicol Lab, Blacksburg, VA 24061 USA Virginia Polytech Inst & State Univ Blacksburg VA USA 24061 VA 24061 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 61, anno: 2001,
pagine: 100 - 106
SICI:
1096-6080(200105)61:1<100:NOTOIH>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENVIRONMENTAL RISK-FACTORS; PARKINSONS-DISEASE; CAUDATE-NUCLEUS; MITOCHONDRIAL RESPIRATION; RAT; EXPOSURE; BRAIN; SYNAPTOSOMES; TRANSPORTER; ENDOSULFAN;
Keywords:
dopamine; dopamine uptake; dopamine release; respiration; cyclodiene; Parkinsonism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Bloomquist, JR Virginia Polytech Inst & State Univ, Dept Entomol, Neurotoxicol Lab, 216 Price Hall, Blacksburg, VA 24061 USA Virginia Polytech Inst &State Univ 216 Price Hall Blacksburg VA USA 24061
Citazione:
M.L. Kirby et al., "Neurotoxicity of the organochlorine insecticide heptachlor to murine striatal dopaminergic pathways", TOXICOL SCI, 61(1), 2001, pp. 100-106

Abstract

Changes in biochemical status of nerve terminals in the corpus striatum, one of the primary brain regions affected in Parkinson's disease, were studied in groups of C57BL/6 mice treated by ip injection three times over a 2-week period with 3-100 mg/kg heptachlor. On average, the maximal rate of striatal dopamine uptake increased > 2-fold in mice treated at doses of 6 mg/kg heptachlor and 1.7-fold at 12 mg/kg heptachlor, Increases in maximal rateof striatal dopamine uptake were attributed to induction of the dopamine transporter (DAT) and a compensatory response to elevated synaptic levels ofdopamine. Significant increase in V-max of striatal DAT was not observed at doses > 12 mgnig, which suggested that toxic effects of heptachlor epoxide may be responsible for loss of maximal dopamine uptake observed at higherdoses of heptachlor. In support of this conclusion, polarigraphic measurements of basal synaptosomal respiration rates from mice treated with doses of heptachlor > 25 mg/kg indicated marked, dose-dependent depression of basal tissue;respiration, At doses of 6 and 12 mg/kg heptachlor, which increased expression of striatal DAT, uptake of 5-hydroxytryptamine into cortical synaptosomes was unaffected. Thus, striatal dopaminergic nerve terminals were found to be differentially sensitive to heptachlor. This reduced sensitivity of serotonergic pathways was mirrored in the greater potency of heptachlor epoxide to cause release of dopamine from preloaded striatal synaptosomes in vitro compared to release of serotonin from cortical membranes. Theseresults suggest that heptachlor, and perhaps other organochlorine insecticides, exert selective effects on striatal dopaminergic neurons and may playa role in the etiology of idiopathic Parkinson's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/06/19 alle ore 17:45:40