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Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson's disease.
Neuroscience. 2006 Sep 15; 141(4):2155-65.N

Abstract

A deficiency of the dopaminergic transmission in the mesocortical system has been suggested to contribute to cognitive disturbances in Parkinson's disease. Therefore, the aim of the present study was to examine whether the long-term administration of a commonly used herbicide, paraquat, which has already been found to induce a slowly progressing degeneration of the nigrostriatal neurons, influences mesocortical dopaminergic neurons in rats. Paraquat at a dose of 10 mg/kg i.p. was injected either acutely or once a week for 4, 8, 12 and 24 weeks. Acute treatment with this pesticide increased the level of homovanillic acid (HVA) and HVA/dopamine ratio in the prefrontal cortex. After 8 weeks of administration paraquat increased the number of stereologically counted tyrosine hydroxylase-immunoreactive (TH-ir) neurons and their staining intensity in the ventral tegmental area (VTA), which is a source of the mesocortical dopaminergic projection. At the same time, few TH-ir neurons appeared in different regions of the cerebral cortex: in the frontal, cingulate, retrosplenial and parietal cortices. Chronic paraquat administration did not influence the level of dopamine in the prefrontal cortex but increased the levels of its metabolites: 3,4-dihydroxyphenylacetic acid (after 8-12 weeks), HVA (after 4 and 12 weeks) and HVA/dopamine ratio (4 weeks). After 24 weeks this pesticide reduced the number of TH-ir neurons in the VTA by 42% and of the Nissl-stained neurons by 26%, and induced shrinkage of this structure by ca. 25%. Moreover, TH-ir neurons in the cortex were no more visible after such a long period of administration and levels of dopamine metabolites returned to control values. The present results suggest that the long-term paraquat administration destroys dopaminergic neurons of the VTA. However, compensatory activation of the VTA neurons and cortex overcomes progressing degeneration and maintains cortical dopaminergic transmission.

Authors+Show Affiliations

Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., PL-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)

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

Language

eng

PubMed ID

16797138

Citation

Ossowska, K, et al. "Degeneration of Dopaminergic Mesocortical Neurons and Activation of Compensatory Processes Induced By a Long-term Paraquat Administration in Rats: Implications for Parkinson's Disease." Neuroscience, vol. 141, no. 4, 2006, pp. 2155-65.
Ossowska K, Smiałowska M, Kuter K, et al. Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson's disease. Neuroscience. 2006;141(4):2155-65.
Ossowska, K., Smiałowska, M., Kuter, K., Wierońska, J., Zieba, B., Wardas, J., Nowak, P., Dabrowska, J., Bortel, A., Biedka, I., Schulze, G., & Rommelspacher, H. (2006). Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson's disease. Neuroscience, 141(4), 2155-65.
Ossowska K, et al. Degeneration of Dopaminergic Mesocortical Neurons and Activation of Compensatory Processes Induced By a Long-term Paraquat Administration in Rats: Implications for Parkinson's Disease. Neuroscience. 2006 Sep 15;141(4):2155-65. PubMed PMID: 16797138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: implications for Parkinson's disease. AU - Ossowska,K, AU - Smiałowska,M, AU - Kuter,K, AU - Wierońska,J, AU - Zieba,B, AU - Wardas,J, AU - Nowak,P, AU - Dabrowska,J, AU - Bortel,A, AU - Biedka,I, AU - Schulze,G, AU - Rommelspacher,H, Y1 - 2006/06/22/ PY - 2006/04/06/received PY - 2006/05/18/revised PY - 2006/05/18/accepted PY - 2006/6/27/pubmed PY - 2006/12/9/medline PY - 2006/6/27/entrez SP - 2155 EP - 65 JF - Neuroscience JO - Neuroscience VL - 141 IS - 4 N2 - A deficiency of the dopaminergic transmission in the mesocortical system has been suggested to contribute to cognitive disturbances in Parkinson's disease. Therefore, the aim of the present study was to examine whether the long-term administration of a commonly used herbicide, paraquat, which has already been found to induce a slowly progressing degeneration of the nigrostriatal neurons, influences mesocortical dopaminergic neurons in rats. Paraquat at a dose of 10 mg/kg i.p. was injected either acutely or once a week for 4, 8, 12 and 24 weeks. Acute treatment with this pesticide increased the level of homovanillic acid (HVA) and HVA/dopamine ratio in the prefrontal cortex. After 8 weeks of administration paraquat increased the number of stereologically counted tyrosine hydroxylase-immunoreactive (TH-ir) neurons and their staining intensity in the ventral tegmental area (VTA), which is a source of the mesocortical dopaminergic projection. At the same time, few TH-ir neurons appeared in different regions of the cerebral cortex: in the frontal, cingulate, retrosplenial and parietal cortices. Chronic paraquat administration did not influence the level of dopamine in the prefrontal cortex but increased the levels of its metabolites: 3,4-dihydroxyphenylacetic acid (after 8-12 weeks), HVA (after 4 and 12 weeks) and HVA/dopamine ratio (4 weeks). After 24 weeks this pesticide reduced the number of TH-ir neurons in the VTA by 42% and of the Nissl-stained neurons by 26%, and induced shrinkage of this structure by ca. 25%. Moreover, TH-ir neurons in the cortex were no more visible after such a long period of administration and levels of dopamine metabolites returned to control values. The present results suggest that the long-term paraquat administration destroys dopaminergic neurons of the VTA. However, compensatory activation of the VTA neurons and cortex overcomes progressing degeneration and maintains cortical dopaminergic transmission. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16797138/Degeneration_of_dopaminergic_mesocortical_neurons_and_activation_of_compensatory_processes_induced_by_a_long_term_paraquat_administration_in_rats:_implications_for_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -