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?

European Journal of Neuroscience - Tập 22 Số 6 - Trang 1294-1304 - 2005
K Ossowska1, Jadwiga Wardas1, Maria Śmiałowska2, Katarzyna Kuter1, Tomasz Lenda1, Joanna M. Wierońska2, Barbara Zięba2, Przemysław Nowak3, Jolanta Dąbrowska3, Aleksandra Bortel3, Adam Kwieciński3, S Wolfarth1
1Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343 Kraków, Poland
2Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, 12, Smętna St., 31-343 Kraków, Poland
3Department of Pharmacology, Medical University of Silesia, 19 H. Jordana St., 41‐808 Zabrze, Poland

Tóm tắt

AbstractThe 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 ≈ 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.

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Tài liệu tham khảo

10.1016/j.sleep.2003.10.013

10.1046/j.1471-4159.2003.01773.x

10.1007/s00441-004-0956-9

10.1016/S0006-8993(98)01192-5

10.1136/bmj.1.5498.1272

10.1046/j.1471-4159.2001.00096.x

10.1016/0272-0590(90)90246-G

10.1007/BF01485901

10.1016/0006-8993(88)91063-3

10.1016/S0940-2993(11)80056-4

10.1016/S1471-1931(00)00019-7

10.1007/BF01291788

10.1111/j.1365-2818.1987.tb02837.x

10.1006/abbi.1996.9726

10.1002/ajim.4700170307

10.1212/WNL.51.2_Suppl_2.S2

10.1016/1055-8330(95)90015-2

10.1006/exnr.1994.1039

Koller W.C., 1992, When does Parkinson's disease begin?, Neurology, 42, 27

10.1038/227680a0

10.1126/science.6823561

10.1016/0304-3940(88)90002-X

10.1212/WNL.48.6.1583

10.1016/S0378-4347(00)84308-X

10.1074/jbc.C100560200

10.1006/nbdi.2002.0507

10.1007/BF01253106

10.1016/0304-3940(85)90424-0

Ossowska K., 2005, The influence of paraquat on dopaminergic transporter in rats, Pharmacol. Reports, 57, 342

10.1016/S0006-8993(01)02601-4

10.1126/science.283.5400.401

10.1016/0006-8993(91)91444-6

10.1016/S0304-3940(98)00198-0

10.1016/0006-8993(83)90993-9

10.1080/10298420290007574

10.1016/S0006-8993(03)02750-1

10.1016/S0168-0102(03)00163-9

10.1016/S0006-8993(01)02577-X

10.1080/10408447609164020

10.1111/j.1365-2818.1984.tb02501.x

10.1016/S0006-8993(00)02496-3

10.1046/j.1460-9568.2003.02781.x

10.1111/j.0953-816X.2004.03139.x

10.1523/JNEUROSCI.20-24-09207.2000

10.1016/0014-5793(81)80112-3

10.1016/S0006-8993(02)02363-6

10.1016/0306-4522(96)00418-6

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European Journal of Neuroscience

Tập 22 Số 6

1294-1304

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