Objectives: Many reports have demonstrated the strong relationship between environmental exposure during the first stages of life and the development in adult phase of neurodegenerative disorders. Previous studies performed in rats exposed from postnatal day 6 to 21 to low dose of permethrin (PERM) induced Parkinson-like neurodegeneration characterized in the striatum by a decrease of Nurr1 gene and protein expression, reduced dopamine level, together with its accelerated turnover (1-3). α-Synuclein is a presynaptic neuronal protein that contributes to Parkinson pathogenesis through its aggregation in oligomeric conformations called protofibrils that mediate disruption of cellular homeostasis and neuronal death. The present work aims to analyze in the striatum of early PERM treated rats the -sinuclein content in the adolescent, adult and old rats. Methods PERM was dissolved in corn oil and administered orally to Wistar rats for 15 days, once a day in the morning from PND6 to PND21. Control rats were treated with vehicle (corn oil 4 ml/kg) on a similar schedule. Rats were sacrificed after 90 days (adolescent age), 180 days (adult age) and 300 days (old age) from the treatment and the striatum collected and kept at -80°C. Tissue lysates were prepared using two different buffers that solubilize -sinuclein in the free and aggregated forms. 40 g of protein were used for western blot analysis, separated using SDS–PAGE (7,5%) and electrophoretically blotted on a nitrocellulose support (Hybond C, Amersham Bioscience, Little Chalfont, UK). -synuclein antibody was purchased by Santa Cruz. Results -synuclein free resulted more expressed in striatum from adolescent treated rats with respect to control while in samples from adult and old rats we observed an opposite situation with decreased level of -sinuclein in treated respect to their controls. Different oligomeric conformations of the protein were also observed when we analyzed by western blotting the lysate with solubilised aggregated protein. Striatum from adolescent treated rats shows higher expression of protein respect to the control with the formations of oligomers Conclusions The early life treatment with PERM induces more significant effect on adolescent rats with the increase of -synuclein in both form, free and aggregated. This behavior could be explained with a more effective impairment of dopaminergic system in the first important phase of the life such as adolescence. References: 1) Carloni M et al. 2012, Exp Gerontol. 47(1):60-66 2) Nasuti C et al.2013, Toxicology 303:162-168 3) Nasuti C et al. 2007, Toxicology 229(3):194-205
Early life permethrin treatment induces in striatum of older rats changes in alpha-synuclein content
FEDELI, Donatella;MONTANI, Maura;NASUTI, Cinzia Carla;GABBIANELLI, Rosita
2014-01-01
Abstract
Objectives: Many reports have demonstrated the strong relationship between environmental exposure during the first stages of life and the development in adult phase of neurodegenerative disorders. Previous studies performed in rats exposed from postnatal day 6 to 21 to low dose of permethrin (PERM) induced Parkinson-like neurodegeneration characterized in the striatum by a decrease of Nurr1 gene and protein expression, reduced dopamine level, together with its accelerated turnover (1-3). α-Synuclein is a presynaptic neuronal protein that contributes to Parkinson pathogenesis through its aggregation in oligomeric conformations called protofibrils that mediate disruption of cellular homeostasis and neuronal death. The present work aims to analyze in the striatum of early PERM treated rats the -sinuclein content in the adolescent, adult and old rats. Methods PERM was dissolved in corn oil and administered orally to Wistar rats for 15 days, once a day in the morning from PND6 to PND21. Control rats were treated with vehicle (corn oil 4 ml/kg) on a similar schedule. Rats were sacrificed after 90 days (adolescent age), 180 days (adult age) and 300 days (old age) from the treatment and the striatum collected and kept at -80°C. Tissue lysates were prepared using two different buffers that solubilize -sinuclein in the free and aggregated forms. 40 g of protein were used for western blot analysis, separated using SDS–PAGE (7,5%) and electrophoretically blotted on a nitrocellulose support (Hybond C, Amersham Bioscience, Little Chalfont, UK). -synuclein antibody was purchased by Santa Cruz. Results -synuclein free resulted more expressed in striatum from adolescent treated rats with respect to control while in samples from adult and old rats we observed an opposite situation with decreased level of -sinuclein in treated respect to their controls. Different oligomeric conformations of the protein were also observed when we analyzed by western blotting the lysate with solubilised aggregated protein. Striatum from adolescent treated rats shows higher expression of protein respect to the control with the formations of oligomers Conclusions The early life treatment with PERM induces more significant effect on adolescent rats with the increase of -synuclein in both form, free and aggregated. This behavior could be explained with a more effective impairment of dopaminergic system in the first important phase of the life such as adolescence. References: 1) Carloni M et al. 2012, Exp Gerontol. 47(1):60-66 2) Nasuti C et al.2013, Toxicology 303:162-168 3) Nasuti C et al. 2007, Toxicology 229(3):194-205I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
