The gestational environment and Parkinson's disease: evidence for neurodevelopmental origins of a neurodegenerative disorder.
Parkinson's Disease (PD) is a degenerative neurological disorder that typically manifests symptoms in late adulthood, after loss of dopaminergic neurons in the nigrostriatal system. A lack of heritability for idiopathic PD has implicated adulthood environmental factors in the etiology of the disease. However, compelling evidence from animal models published within the past few years has shown that a range of environmental factors occurring during the perinatal period (including exposure to the common pesticides paraquat and maneb, organochlorine pesticides, and iron-enriched diet) and the prenatal period (including the pesticide maneb, cocaine, and the bacterial product LPS) can either directly cause a reduction in the number of dopamine neurons, or cause an increased susceptibility to degeneration of these neurons with subsequent environmental insults or with aging alone. In this review, these models are described for potential relevance in linking PD with the Fetal Basis of Adult Disease (FeBAD) hypothesis. Additionally, challenges in studying the neurodevelopmental basis of neurodegeneration experimentally and epidemiologically are presented.
Barlow
Brian K
BK
MD/PhD Program, Graduate Program in Neuroscience, UMDNJ-RWJMS and Rutgers, USA.
Cory-Slechta
Deborah A
DA
Richfield
Eric K
EK
Thiruchelvam
Mona
M
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D004298:Dopamine