Protective role of 6-Hydroxy-1-H-Indazole in an MPTP-induced mouse model of Parkinson's disease

Abstract

This study aimed to explore the neuroprotective role of 6-hydroxy-1H-indazole on dopaminergic neurons in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Forty 12-week-old C57BL/6 male mice were were randomized divided into 4 groups. Mice were treated with 2mg/kg and 4mg/kg 6-hydroxy-1H-indazole (i.p.) 1d before the initiation of MPTP administration (30mg/kg), and the 6-hydroxy-1H-indazole were daily injected half an hour before MPTP treatment in the following 5 days. The MPTP group was given normal saline on day 1 (i.p.), followed by 30mg/kg MPTP treatment in the following 5 days. Control group received an equivalent volume of normal saline. Ten days after the final injection of MPTP, the mice were killed. The results showed that MPTP decreased the dopaminergic neurons in the substantia nigra and dopamine in the striatum, downregulated the expression of tyrosine hydroxylase (TH), induced the impairment of behavior and hyperphosphorylation of tau, However, 6-hydroxy-1-H-indazole decreased the loss of dopaminergic neurons, increased dopamine concentration and TH expression, alleviated the behavioral damage and level of phosphor-tau in the MPTP-induced model of PD in C57BL/6 mice. These findings showed that 6-hydroxy-1-H-indazole-mediated neuroprotection was related to the inactivation of tau. In addition, 6-hydroxy-1-H-indazole may be a potential drug candidate for PD.

Keywords: 6-Hydroxy-1H-indazole (PubChem CID: 254509318); 6-hydroxy-1-H-indazole; Dopaminergic neurons; MPTP; Parkinson's disease; Tau.