[Abstract Title]. - Society for Neuroscience

DGAPA IN-214607-3
Title: Rotenone-induced nigrostriatal dopaminergic neurons degeneration during early
development stages in rats
Authors: *M. GOMEZ-CHAVARIN 1 , R. MORALES 2 , M. C. RAMIREZ 3 , G. ROLDAN 1 , J.
FERNANDEZ 1 ;
1 Dept. de Fisiología, UNAM, Mexico D. F., Mexico; 2 Dept. de Microbiología y Parasitología
Facultad de Medicina, UNAM, D.F., Mexico; 3 Dept. de Sistemas Biológicos, UAM-Xochimilco,
D.F., Mexico
Abstract: INTRODUCTION Epidemiological studies have linked environmental factors with
increased risk of idiopathic Parkinson‟s disease (PD). Because PD is associated with a late-in-life
onset, it has traditionally been considered as a disease of aging, despite a long history of
speculation that environmental factors early in life can predispose an individual to develop
parkinsonian symptoms. Recent reports have begun to identify specific environmental factors
occurring in uterus or during perinatal development that may prompt nigrostriatal system
damage. Rotenone (ROT) is a commonly used pesticide that has been associated with
parkinsonism since it produces degeneration of dopaminergic neurons (DAN) at the nigrostriatal
pathway. Chronic exposure to ROT in adult rats induces nigrostriatal DAN degeneration
accompanied by aggregation of α-synuclein (α-syn) and motor deficits. OBJETIVE To analyze
the effect of a low dose ROT treatment during gestation and/or nursing on biochemical markers
associated with PD in adulthood. METHODS Pregnant Wistar rats were s.c administrated. with
250 κg/day of ROT. One day after birth, offspring were divided in 3 groups: 1) Gestation
Group which received ROT only during gestation phase and was nursed by an intact fostermother
which has never been exposed to ROT, 2) Nursing Group which received ROT only
during lactation thought a ROT-treated rat, and 3) Gestation/Nursing Group which received
ROT during both stages. Offspring were sacrificed at the 15, 30 or 60 postnatal day and their
brains were processed for tyrosine hydroxilase (TH) immunostain. In a second experiment, other
three groups treated as described above were evaluated for motor activity and α-syn content in
the striatum and substantia nigra, two months after birth. RESULTS All ROT-treated groups
showed motor deficits and a progressive decrease in TH+ neurons in the substantia nigra, plus an
increase in α-syn aggregation into striatum and substantia nigra which was highest in
Gestation/Nursing Group. CONCLUSIONS The results show a deleterious effect of low doses
ROT treatment during early stages of life. These effects were progressive, irreversible and more
severe when the exposure to ROT occurred during gestation than during nursing, suggesting that
the nigrostriatal system is more vulnerable at this phase. Therefore, exposure to xenobiotics
during early stages of life should be considered in the etiology of neurodegenerative disorders in
adulthood.
Disclosures: M. Gomez-Chavarin, None; R. Morales, None; M.C. Ramirez, None; G.
Roldan, None; J. Fernandez, None.