Chenodeoxycholic Acid-Mediated neuroprotection via α-synuclein and BDNF Modulation in MPTP-Induced mouse model of Parkinson's disease

Abstract

Parkinson's disease (PD) remains a major challenge in the field of neurodegenerative diseases and requires innovative therapeutic approaches. In this study, we investigated the therapeutic potential of chenodeoxycholic acid (CDCA) in PD using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. CDCA, a naturally occurring bile acid, has previously shown promise in various neurological disorders by reducing neuronal degeneration and promoting neuronal health, however its utility in PD has not been studied. We divided mice into a control group, an MPTP-induced PD model and a treatment group injected with CDCA. CDCA reduced motor impairment and ameliorated anxiety-like behavior as assessed through the pole and open field test, demonstrated antidepressant effects in the forced swim and tail suspension test, and results of the Y-maze test showed improved cognitive performance. Furthermore, the effective defense against MPTP-induced dopaminergic degeneration was provided by CDCA by improving the morphological and histological features of neurons in the midbrain, hippocampus, cortex and cerebellum. Analysis via RT-PCR revealed that CDCA significantly mitigated MPP + -induced elevations in α-synuclein levels, indicating its potential to preserve neuronal function by modulating synaptic integrity. Additionally, CDCA effectively reduced the associated toxicity by enhancing the low levels of brain-derived neurotrophic factor. Conclusively, given the increasing prevalence of PD and the urgent need for effective neuroprotective strategies, our findings suggest that CDCA exerts neuroprotective effects in an MPTP-induced PD model. These results highlight CDCA as a promising candidate for further investigation in PD therapy and provide a basis for further research into bile acid-based treatments in neurodegenerative diseases.

Keywords: BDNF; Chenodeoxycholic acid; MPTP; Parkinson’s disease; α-synuclein.