Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates

摘要: Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have critical role. Our previous studies instigated novel PD model based on nasal inoculation with α-syn aggregates expressed parkinsonian-like behavioral immunological features. The current study mice substantiated the robustness of amyloid vector by examining consequences respect to DA-ergic neurochemical corollaries. In vitro generated oligomers fibrils were characterized using atomic force microscopy thioflavin T binding assay. These toxic or administered alone (0.48 mg/kg) their 50:50 combination (total dose 0.48 given intranasally for 14 days “open-field” behavior was tested 0, 15 28 protocol. Behavioral deficits at end 14-day dosing regime day (i.e., after treatment completion) induced rigidity, hypokinesia immobility. This accompanied elevated nigral but not striatal DA, DOPAC HVA concentrations response dual administration plus themselves. α-Syn intensified only immobility post treatment, also reduced vertical rearing enhanced DA levels substantia nigra. Only turnover (DOPAC/DA HVA/DA ratio) augmented fibril there no changes striatum. Compilation these findings substantiate validity investigating symptoms.