Evaluation of Carnosine Intervention in the Thy1-aSyn Mouse Model of Parkinson's Disease

摘要

Parkinson disease (PD) is a leading neurodegenerative disease, with multifaceted interacting mechanisms. The Thy1-aSyn mouse model of PD exhibits many features of PD patients, including sensorimotor and olfactory dysfunction and protein aggregation. Here, we tested the hypothesis that the dipeptide carnosine, which has anti-aggregating and metal-chelating properties, would provide beneficial effects on the motor and olfactory deficits observed in Thy1-aSyn mice. After 2 months of daily treatment with either intranasal (2 mg/day) or oral (10 mM in drinking water) carnosine, Thy1-aSyn mice and wild-type BDF1 mice were assessed for sensorimotor (challenging beam traversal test and spontaneous activity) and olfactory (buried pellet test) function. In addition, the olfactory epithelium was evaluated immunohistochemically for expression of alpha-synuclein (aSyn) and the carnosine transporter Pept2. Olfactory function was unaffected by carnosine treatment via either administration route. In contrast, intranasal carnosine prevented the normal decline in gait function seen in the challenging beam test in the Thy1-aSyn mice. Moreover, carnosine-treated Thy1-aSyn mice exhibited decreased aSyn immunostaining in the olfactory epithelium compared to vehicle-treated Thy1-aSyn mice, and the carnosine transporter Pept2 was immunolocalized to the apical surface of the olfactory epithelium. These findings demonstrate that intranasal carnosine shows promise in slowing the progression of motor deficits and aSyn deposition in PD. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.