Protective Effect of CP690550 in MPTP-Induced Parkinson's Like Behavioural, Biochemical and Histological Alterations in Mice

Abstract

Janus-activated kinases (JAKs) are well known to play a physiological as well as pathological role in several disease conditions such as autoimmune disorders. The present study evaluated the therapeutic potential of CP690550 (pan-JAK inhibitor) in 1-methyl-4-phenyl-1,2,3,6-tertahydropyridine (MPTP) model of Parkinson's disease. Intrastriatal administration of MPTP (30 micromol in 2 microl) produced a significant alteration in behavioural (bar test and block test). Biochemical investigations in serum and brain homogenate revealed a significant alteration in the JAK-mediated cytokine levels. MPTP administration also showed significant imbalance of inflammatory (increased TNF-α, IL-6 and NF-κb) versus anti-inflammatory cytokines (decreased IL-10 levels). MPTP-treated brain sections revealed alteration in the tissue architecture as well as undifferentiated bodies of varying contour and lesions. Chronic administration of CP690550 (3 and 10 mg/kg, po) for 7 days significantly reversed the behavioural, biochemical and histological alterations induced by MPTP. In conclusion, the findings of the present study govern the possible therapeutic potential of CP690550 in MPTP-treated mice and thus highlight the therapeutic potential of JAK inhibitors in treatment of Parkinson's disease.

Keywords: Astrocytes; Dopaminergic neurons; JAKs; Microglia; Parkinson disease.