Degeneration of dopaminergic mesocortical neurons and activation of compensatory processes induced by a long-term paraquat administration in rats: Implications for Parkinson’s disease

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 al...

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Published in:Neuroscience 2006-01, Vol.141 (4), p.2155-2165
Main Authors: Ossowska, K., Śmiałowska, M., Kuter, K., Wierońska, J., Zięba, B., Wardas, J., Nowak, P., Dąbrowska, J., Bortel, A., Biedka, I., Schulze, G., Rommelspacher, H.
Format: Article
Language:English
Subjects:
3,4-Dihydroxyphenylacetic Acid - metabolism
Animals
Behavior, Animal - drug effects
Biological and medical sciences
Cerebral Cortex - cytology
Chromatography, High Pressure Liquid - methods
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Disease Models, Animal
Dopamine - metabolism
Fundamental and applied biological sciences. Psychology
Herbicides - administration & dosage
Homovanillic Acid - metabolism
Immunohistochemistry - methods
Male
Medical sciences
Nerve Degeneration - chemically induced
Nerve Degeneration - metabolism
Nerve Degeneration - pathology
Nerve Degeneration - physiopathology
Neurology
Neurons - drug effects
Paraquat - administration & dosage
Parkinsonian Disorders - chemically induced
Parkinsonian Disorders - pathology
Parkinsonian Disorders - physiopathology
prefrontal cortex
Rats
Rats, Wistar
stereology
striatum
Tyrosine 3-Monooxygenase - metabolism
tyrosine hydroxylase-immunoreactive neurons
ventral tegmental area
Ventral Tegmental Area - metabolism
Ventral Tegmental Area - pathology
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2006.05.039