Studio della trasmissione dopaminergica e del metabolismo energetico striatale in modelli animali di Parkinson

Parkinson’s desease (PD) is characterized by a selective loss of neurons in the substantia nigra pars compacta and a significant reduction of neostriatal content of dopamine (DA) and its major acidic metabolites DOPAC and homovanillic acid. MPTP is known to cause parkinsonism in human and this fact is a major incentive for using this toxin as an animal model of PD. In this study C57BL/6 mice were given MPTP in a sub-acute regimen, that induce tissue striatal DA depletion and nigral neuron death, and sub-chronic regimen, that induce in freely moving mice behavioural impairment and prolonged release of striatal DA. Such DA release may be considered the first step in MPTP-induced striatal DA depletion. Wistar rats were given MPTP for 3 consecutive days (respectively 25, 15, 10 mg/Kg/day) to study, by microdialysis, DA depletion, energetic metabolism and energy requirements during neuronal activation. Sistemically-administered MPTP induced a decrese in striatal glucose level and an increse in lactate and lactate/pyruvate (L/P) ratio levels in contrast with damphetamine that not affect L/P ratio. A new α-synuclein based model of PD in Wistar rats, more stable than MPTP model, has been proposed as a new frontier to evaluate the potential role of adult stem cells in an attempt of restorative therapy in PD.