2013, Number 1
Next >>
Salud Mental 2013; 36 (1)
Efecto de la exposición al pesticida rotenona sobre el desarrollo del sistema dopaminérgico nigro-estriatal en ratas
Gómez-Chavarín M, Díaz-Pérez R, Morales-Espinosa R, Fernández-Ruiz J, Roldán-Roldán G, Torner C
Language: Spanish
References: 33
Page: 1-8
PDF size: 330.63 Kb.
ABSTRACT
Rotenone is a pesticide used in Mexico, despite the experimental evidence showing dopaminergic neurons degeneration induced by this compound, which may lead to a psychomotor impairment. However, the possible effects of rotenone on the offspring when they are indirectly exposed through their mothers are still unknown. In this study rotenone was administered to female rats during pregnancy and nursing, in order to assess its effects on the offspring’s dopaminergic neurons in the substantia nigra, as well as on motor coordination at 30 or 60 postnatal days.
Six groups of pregnant Wistar rats were used: an intact control group, a vehicle group injected with the rotenone solvent, and four groups injected subcutaneously with the following doses of rotenone: 0.2, 0.4, 0.6, and 1 mg/kg/day. In a parallel experiment, the offspring of other groups of dams treated with rotenone 1 mg/kg/day, or controls vehicle-treated, were used to evaluate motor coordination at 30 and 60 postnatal days.
Rotenone treated dams showed a significant lower amount of dopaminergic neurons in the substantia nigra, but only with the 1 mg/kg dose. This effect was also observed in the offspring but at all doses of rotenone tested, either at 30 or 60 postnatal days. Furthermore, the offspring of rotenone exposed dams significantly increased the time in which they accomplished the motor coordination test, compared to the offspring of control dams.
These data indicate that rotenone is able to damage the dopaminergic neurons of the offspring though their mothers. This effect requires lower rotenone doses than in adult rats. The reduced number of dopaminergic neurons at early stages of life enhances the risk of developing disorders related to the brains’ dopaminergic system.
REFERENCES
Kilbourn MR, Charalambous A, Frey KA, Sherman P et al. Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I. J Cereb Blood Flow Metab 1997;17(3):265-272.
Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 2000;3(12):1301-1306.
Dhillon AS, Tarbutton GL, Levin JL, Plotkin GM et al. Pesticide/environmental exposures and Parkinson’s disease in East Texas. J Agromedicine 2008;13(1):37-48.
Vanacore N, Nappo A, Gentile M, Brustolin A et al. Evaluation of risk of Parkinson’s disease in a cohort of licensed pesticide users. Neurol Sci 2002;23(2):S119-5120.
Moretto A, Colosio C. Biochemical and toxicological evidence of neurological effects of pesticides: The example of Parkinson’s disease. Neurotoxicology 2011;32(4):383-391.
Wang A, Costello S, Cockburn M, Zhang X et al. Parkinson’s disease risk from ambient exposure to pesticides. Eur J Epidemiol 2011;26(7):547-555.
Sherer TB, Kim JH, Betarbet R, Greenamyre JT. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 2003;179(1):9-16.
Schapira AH, Cooper JM, Dexter D, Jenner P et al. Mitochondrial complex I deficiency in Parkinson’s disease. Lancet 1989;1(8649):1269.
Paxinos G, Watson Ch. The rat brain in stereotaxic coordinates. San Diego: Academic Press; 1997.
Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet 2006;368(9553):2167-2178.
Brown TP, Rumsby PC, Capleton AC, Rushton L et al. Pesticides and Parkinson’s disease- is there a link? Environ Health Perspect 2006;114(2):156-164.
Trash B, Uthayathas S, Karuppagounder SS, Suppiramaniam V et al. Paraquat and maneb induced neurotoxicity. Proc West Pharmacol Soc 2007;50:31-42.
Barlow BK, Cory-Slechta DA, Richfield EK, Thiruchelvam M. The gestational environment and Parkinson’s disease: evidence for neurodevelopmental origins of a neurodegenerative disorder. Reprod Toxicol 2007;23(3):457-470.
Wigle DT, Arbuckle TE, Walker M, Wade MG et al. Enviromental hazards: Evidence for efectos on child health. J Toxicol Envir Health Part B 2007;10:3–39.
Alam M, Schmidt WJ. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav Brain Res 2002;136(1):317-324.
Fleming SM, Zhu C, Fernagut PO, Mehta A et al. Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp Neurol 2004;187(2):418-429.
Luo C, Rajput AH, Akhtar S, Rajput A. Alpha-synuclein and tyrosine hydroxylase expression in acute rotenone toxicity. Int J Mol Med 2007;19(3):517-521.
Cannon JR, Tapias V, Na HM, Honick AS et al. A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 2009;34(2):279-290.
Thiruchelvam M, Richfield EK, Goodman BM, Baggs RB et al. Developmental exposure to the pesticides paraquat and maneb and the Parkinson’s disease phenotype. Neurotoxicology 2002;23(4-5):621-633.
Cory-Slechta DA, Thiruchelvam M, Barlow BK, Richfield EK. Developmental pesticide models of the Parkinson disease phenotype. Environ Health Perspect 2005;113(9):1263-1270.
Cicchetti D, Walker E. Neurodevelopmental Mechanisms in Psychopathology. Cambridge University Press; 2003.
Julvez J, Grandjean P. Neurodevelopmental toxicity risks due to occupational exposure to industrial chemicals during pregnancy. Ind Health 2009;47(5):459-468.
Eriksson P. Developmental neurotoxicity of environmental agents in the neonate. Neurotoxicology 1997;18(3):719-726.
Heindel JJ. The fetal basis of adult disease: Role of environmental exposures-introduction. Birth Defects Res A Clin Mol Teratol 2005;73(3):131-132.
Landrigan PJ, Sonawane B, Butler RN, Trasande L et al. Early environmental origins of neurodegenerative disease in later life. Environ Health Perspect 2005;113(9):1230-1233.
Richardson JR, Caudle WM, Wang M, Dean ED et al. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson’s disease. FASEB J 2006;20(10):1695-1697.
Mehler-Wex C, Riederer P, Gerlach M. Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for the pathophysiology of Parkinson’s disease, schizophrenia and attention deficit hyperactivity disorder. Neurotox Res 2006;10(3-4):167-179.
Kuehn BM. Increased risk of ADHD associated with early exposure to pesticides, PCBs. JAMA 2010;304(1):27-28.
Warton FL, Howells FM, Russell VA. Increased glutamate-stimulated release of dopamine in substantia nigra of a rat model for attentiondeficit/hyperactivity disorder-lack of effect of methylphenidate. Metab Brain Dis 2009;24(4):599-613.
Wirdefeldt K, Adami HO, Cole P, Trichopoulos D et al. Epidemiology and etiology of Parkinson’s disease: a review of the evidence. Eur J Epidemiol 2011;26 (Supl 1):S1-58.
Whatley SA, Curti D, Marchbanks RM. Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res 1996;21(9):995-1004.
Santiago RM, Barbieiro J, Lima MM, Dombrowski PA et al. Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson’s disease are predominantly associated with serotonin and dopamine. Prog Neuropsychopharmacol Biol Psychiatry 2010;34(6):1104-1114.
Dirección General de Servicios de Salud Mental. Programa de Acciones en Salud Mental. Análisis de la Problemática de la Salud Mental en México. Diagnostico Epidemiológico. Cap. III, Año 2002, págs. 43- 57 (http://sersame.salud.gob.mx/pdf/pasm_cap3.pdf).