Double triggers, nasal induction of a Parkinson's disease mouse model.

• A PD mouse model by double triggered nasal administration with MPTP and LPS is established. • The model displays behavioral, pathological and cytological characteristics of PD. • The model more closely mimics the actual pathogenesis and progressive process of PD. • The model is easy to be prepared and only takes 7 weeks. Animal models of Parkinson's disease (PD), a chronic and progressive neurodegenerative disease of the central nervous system (CNS), play a key role in investigating the pathogenesis and developing new therapeutic strategies of PD. However, this goal has been limited by certain weaknesses in the available animal models of PD, e.g., induction by either pro-inflammatory or neurotoxic reagents, or they are too time-/effort-consuming. Here, we report a double triggers, nasal induction of a PD mouse model that mimics the clinical, pathological features and pathogenesis of PD by intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) combined with lipopolysaccharide (LPS). After administration once every three days for 7 consecutive weeks, these mice displayed enhanced motor dysfunction, loss of dopaminergic neurons, α-synuclein accumulation, as well as activation of microglia and astrocytes in the substantia nigra pars compacta compared with mice that were administered MPTP or LPS alone. This study provides a novel and basic research tool for investigating the pathogenesis and therapeutic intervention of PD. [ABSTRACT FROM AUTHOR]