Behavioral, Biochemical and Molecular Characterization of a Parkinson ’s Disease Mouse Model Using the Neurotoxin 2′-CH 3 -MPTP: A Novel Approach

AbstractThe neurotoxin MPTP has long been used to create a mouse model of Parkinson ’s disease (PD). Indeed, several MPTP analogues have been developed, including 2′-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2 ′-CH3-MPTP has been carried out so far. In the present work, 2 ′-CH3-MPTP was administered to mice (2.5, 5.0 and 10  mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated. We show that, despite a dose-dependent-like pattern observed for nigrostriatal dopaminergic neuronal death and dopamine depletion, dose-specific alterations in dopamine met abolism and in the expression of dopaminergic neurotransmission-associated genes could be related to specific motor deficits elicited by the different doses tested. Interestingly, 2′-CH3-MPTP leads to increased DAT and MAO-B transcription, which could explain, respectively, its higher potency and the requirement of higher doses of MAO inhibitors to prevent nigrostriatal neuronal death when compared to MPTP. Also, perturbations in dopamine metabolism as well as possible alterations in dopamine bioavailability in the synaptic cleft were also identified and correlated with strength and ambulation deficits in response to specific doses. Overall, the present work brings new evidence supporting the distinct effects of 2 ′-CH3-MPT...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research