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Vol. 26, No.
1, 2004
Free Abstract Article (References) Article (PDF 480 KB)
Original
Paper
A Fetal
Risk Factor for Parkinson's Disease
Brian K. Barlowa, Eric K. Richfielda,c, Deborah A. Cory-Slechtab,c, Mona Thiruchelvamb,c
aDepartment of Pathology and
Laboratory Medicine,
bDepartment of Environmental Medicine,
cNIEHS Environmental Health Sciences
Center, University of Rochester School of Medicine and Dentistry,
Rochester, N.Y., USA
Address
of Corresponding Author
Developmental Neuroscience
2004;26:11-23 (DOI: 10.1159/000080707)
 Key
Words
- Maneb
- Paraquat
- Parkinson's
disease
Abstract
A lack of strong evidence for genetic
heritability of idiopathic Parkinson's disease (PD) has focused attention
on environmental toxicants in the disease etiology, particularly
agrichemicals. PD is associated with advanced age, but it is unclear
whether specific neuronal damage could result from insults during
development. This study hypothesized that prenatal exposure to pesticides
would disrupt the development of the nigrostriatal
dopamine (DA) system and enhance its vulnerability to dopaminergic
neurotoxicant exposures later in life. Pregnant
C57BL/6J mice were treated on gestational days 10-17 with saline or the
pesticides maneb (MB, 1 mg/kg) or paraquat (PQ, 0.3 mg/kg). When offspring were evaluated
in adulthood, there were no significant effects of prenatal MB or PQ
exposure on locomotor activity. Subsequently,
offspring were treated for 8 consecutive days with saline, MB (30 mg/kg),
or PQ (5 mg/kg). One week after the last exposure, only males exposed to
prenatal MB and adulthood PQ showed significant reductions in locomotor activity (95%) and changes in striatal neurochemistry. Stereological assessment of
the substantia nigra
pars compacta (SNpc)
and ventral tegmental area correspondingly
confirmed selective dopaminergic-neuron loss in SNpc. The lack of changes in other exposure groups
suggests a specificity to the sequence of exposures as well as gender
specificity. These results suggest that prenatal exposure to MB produces
selective, permanent alterations of the nigrostriatal
dopaminergic system and enhances adult susceptibility
to PQ exposure. This study implicates a role for developmental neurotoxicant exposure in the induction of
neurodegenerative disorders such as PD.
Copyright © 2004 S. Karger
AG, Basel
Author
Contacts
Mona Thiruchelvam,
PhD, Department of Environmental and Community Medicine
UMDNJ Robert Wood Johnson Medical School
Environmental and Occupational Health Sciences Institute
170 Frelinghuysen Road, Piscataway, NJ 08854 (USA)
Tel. +1 732 445 8186, Fax +1 732 445 0131, E-Mail mjt@eohsi.rutgers.edu
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