Alvau, Maria Domenica (2014) Effetti della neurotossina MPTP e protezione da parte della pargilina sui metaboliti energetici extracellulari e sui livelli di dopamina nello striato di ratti "freely moving". Doctoral Thesis.
The neurotoxin MPTP induces neurodegeneration of SNpc dopaminergic cells by mitocondrial impairment. Therefore, we deemed of interest the study of pargyline neuroprotective role on dopamine (DA) and energy metabolism. The study was carried out on Wistar rats using an asymmetric microdialysis allowing simultaneous monitoring of DA and energy substrates striatal levels. Samples were quantified via spectrophotometer and HPLC-EC tecniques. Moreover, amperometric microsensors and biosensors were used to real-time detect oxygen (O2), glucose (GLU) and lactate (LAT) variations. Both microdialisys probes and sensors were stereotaxically implanted in right striatum. Pargyline (15mg/Kg) pre-treatment was injected i.p. for 3 days 40 min before MPTP administration (25/15/10mg/Kg i.p.). First MPTP dose induced an increase of DA and O2 levels among all groups. A decrease of striatal DA levels following further MPTP administrations were observed. This trend was partially contrasted in pargyline pre-treated group. Furthermore, first MPTP dose led to a general increase of striatal energy substrates concentrations, while subsequent toxin administration at days 2 and 3 showed a progressive reduction of GLU and PYR and an increase of LAT striatal levels and L/P ratio. Pargyline pre-treatment partially preserved GLU and PYR decrease, as well as LAT and L/P ratio MPTP-related increase. These results ascertained pargyline neuroprotective effect on DA and energy metabolism by preventing MPTP insult.
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