Chronic inhalation of rotenone or paraquat does not induce Parkinson's disease symptoms in mice or rats.
Epidemiological studies suggest that some pesticides might constitute a risk factor for Parkinson's disease (PD). However, risk assessment cannot be performed in the current experimental animal models because they use non-natural pathways of pesticide exposure, such as intraperitoneal or intravenous injection, that might bypass body defences. A new model based on daily inoculation of neurotoxins in the nasal cavity of C57BL/6 mice for 30 days was used to evaluate risk of three complex I inhibitors, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP), rotenone and paraquat. These compounds displayed very different effects on motor activity, striatal dopamine and dihydroxyphenylacetic acid (DOPAC) levels and loss of dopaminergic neurons. MPTP-treated mice developed motor deficits that correlated with a severe depletion of striatal dopamine levels, and loss of tyrosine hydroxylase staining in substantia nigra and striatum. By contrast, rotenone-treated mice or rats were asymptomatic. Paraquat induced severe hypokinesia and vestibular damage but did not alter the nigrostriatal system. The new animal model described here, based on chronic intranasal inoculation of neurotoxicants, provides a new tool to assess the potential danger of environmental toxins as risk factors for development of PD.
Rojo
Ana I
AI
Instituto de Investigaciones Biomédicas, Departamento de Bioquímica Facultad de Medicina, and Centro de investigación en Red en Enfermedades Neurodegenerativas (CIBERNED), Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Cavada
Carmen
C
de Sagarra
María Rosa
MR
Cuadrado
Antonio
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D006540:Herbicides / Q000008:administration & dosage* / Q000494:pharmacology; D007306:Insecticides / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010269:Paraquat / Q000008:administration & dosage* / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000008:administration & dosage* / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D006540:Herbicides; D007306:Insecticides; D012402:Rotenone; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010269:Paraquat; D004298:Dopamine