Background: In this study, we sought to provide an idea for establishing a novel mouse model for Parkinson's disease (PD) through intranasal administration of paraquat instead of the conventional method of intraperitoneal injection. Intranasal administration has the potential to lower mortality caused by intraperitoneal paraquat administration.Methods: A paraquat-loaded thermosensitive hydrogel composed of poloxamer 407 and poloxamer 188 was prepared. The survival rate of the animals was monitored upon paraquat administration nasally and intraperitoneally. The animals' behavior was also observed. Immunofluorescence staining of tyrosine hydroxylase (TH) - positive cells and western blotting of α-synuclein (α-syn)in striatum were performed. HPLC method with electrochemical detection was used to quantify monoamine neurotransmitters in striatum. Real-time RT-PCR analysis of type 1 collagen, type 3 collagen and fibronectin expression was used to evaluate pulmonary fibrosis in mice after paraquat administration.Results: The results indicated that intranasal administration of paraquat-loaded thermosensitive hydrogel can elicit Parkinsonism-like symptoms in mice. Relative to the conventional intraperitoneal injection, this strategy significantly improves survival when modeling PD and resulted in a higher loss of TH positive neurons in substantia nigra pars compacta (SNpc) and more aggregation of α-syn in striatum. Moreover, animals receiving paraquat hydrogel nasally exhibited motor disorder as well as lower levels of dopamine and dopamine metabolites in striatum when compared to those receiving paraquat intraperitoneally. The mRNA expression of collagen and fibronectinindicated that intranasal administration of paraquat was not associated with lung fibrosis.Conclusion: This strategy provides a new idea and more convenient operation for the future study of mouse model of PD.
Keywords: Parkinson’s disease; animal model; intranasal administration; paraquat.