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A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson's disease?
Eur J Neurosci. 2005 Sep; 22(6):1294-304.EJ

Abstract

The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg/kg i.p. for 4-24 weeks. We found that this pesticide reduced the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra; after the 4-week treatment the reduction (17%, nonsignificant) was confined to the rostrocentral region of this structure but, after 24 weeks, had spread along its whole length and was approximately 37%. Moreover, it induced a biphasic effect on dopaminergic transmission. First, levels of dopamine, its metabolites and turnover were elevated (4-8 weeks) in the caudate-putamen, then all these parameters returned to control values (12 weeks) and dropped by 25-30% after 24 weeks. The binding of [3H]GBR 12,935 to dopamine transporter in the caudate-putamen was decreased after 4-8 weeks, then returned to control values after 12 weeks but was again decreased after 24 weeks. Twenty-four-week paraquat administration also decreased the level of tyrosine hydroxylase (Western blot) in the caudate-putamen. In addition, paraquat activated serotonin and noradrenaline transmission during the first 12 weeks of treatment but no decreases in levels of these neurotransmitters were observed after 24 weeks. The above results seem to suggest that long-term paraquat administration produces a slowly progressing degeneration of nigrostriatal neurons, leading to delayed deficits in dopaminergic transmission, which may resemble early, presymptomatic, stages of Parkinson's disease.

Authors+Show Affiliations

Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 Kraków, Poland. ossowska@if-pan.krakow.plNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16190885

Citation

Ossowska, K, et al. "A Slowly Developing Dysfunction of Dopaminergic Nigrostriatal Neurons Induced By Long-term Paraquat Administration in Rats: an Animal Model of Preclinical Stages of Parkinson's Disease?" The European Journal of Neuroscience, vol. 22, no. 6, 2005, pp. 1294-304.
Ossowska K, Wardas J, Smiałowska M, et al. A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson's disease? Eur J Neurosci. 2005;22(6):1294-304.
Ossowska, K., Wardas, J., Smiałowska, M., Kuter, K., Lenda, T., Wierońska, J. M., Zieba, B., Nowak, P., Dabrowska, J., Bortel, A., Kwieciński, A., & Wolfarth, S. (2005). A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson's disease? The European Journal of Neuroscience, 22(6), 1294-304.
Ossowska K, et al. A Slowly Developing Dysfunction of Dopaminergic Nigrostriatal Neurons Induced By Long-term Paraquat Administration in Rats: an Animal Model of Preclinical Stages of Parkinson's Disease. Eur J Neurosci. 2005;22(6):1294-304. PubMed PMID: 16190885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A slowly developing dysfunction of dopaminergic nigrostriatal neurons induced by long-term paraquat administration in rats: an animal model of preclinical stages of Parkinson's disease? AU - Ossowska,K, AU - Wardas,J, AU - Smiałowska,M, AU - Kuter,K, AU - Lenda,T, AU - Wierońska,J M, AU - Zieba,B, AU - Nowak,P, AU - Dabrowska,J, AU - Bortel,A, AU - Kwieciński,A, AU - Wolfarth,S, PY - 2005/9/30/pubmed PY - 2006/1/13/medline PY - 2005/9/30/entrez SP - 1294 EP - 304 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 22 IS - 6 N2 - The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg/kg i.p. for 4-24 weeks. We found that this pesticide reduced the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra; after the 4-week treatment the reduction (17%, nonsignificant) was confined to the rostrocentral region of this structure but, after 24 weeks, had spread along its whole length and was approximately 37%. Moreover, it induced a biphasic effect on dopaminergic transmission. First, levels of dopamine, its metabolites and turnover were elevated (4-8 weeks) in the caudate-putamen, then all these parameters returned to control values (12 weeks) and dropped by 25-30% after 24 weeks. The binding of [3H]GBR 12,935 to dopamine transporter in the caudate-putamen was decreased after 4-8 weeks, then returned to control values after 12 weeks but was again decreased after 24 weeks. Twenty-four-week paraquat administration also decreased the level of tyrosine hydroxylase (Western blot) in the caudate-putamen. In addition, paraquat activated serotonin and noradrenaline transmission during the first 12 weeks of treatment but no decreases in levels of these neurotransmitters were observed after 24 weeks. The above results seem to suggest that long-term paraquat administration produces a slowly progressing degeneration of nigrostriatal neurons, leading to delayed deficits in dopaminergic transmission, which may resemble early, presymptomatic, stages of Parkinson's disease. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16190885/A_slowly_developing_dysfunction_of_dopaminergic_nigrostriatal_neurons_induced_by_long_term_paraquat_administration_in_rats:_an_animal_model_of_preclinical_stages_of_Parkinson's_disease L2 - https://doi.org/10.1111/j.1460-9568.2005.04301.x DB - PRIME DP - Unbound Medicine ER -