Investigating the Neuroprotective Effects of Chenodeoxycholic Acid in MPTP-induced Parkinson’s disease in BALB/c mice

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. Mice were divided into a control group, an MPTP-induced PD model (20 mg/kg, intraperitoneally) and a treatment group injected intraperitoneally with CDCA (90 mg/kg). CDCA reduced motor impairment and ameliorated anxiety-like behavior as assessed by the pole test and open field test, demonstrated antidepressant effects in the forced swim test 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 through improving the morphological and histological features of neurons in the midbrain, hippocampus, cortex and cerebellum. Additionally, the biomarkers used in this study are brain-derived neurotrophic factor (BDNF) and α-synuclein. Hence, treatment with CDCA significantly mitigated MPTP-induced elevations in α- synuclein levels, indicating that it may have potential to preserve and recover neuronal function. Moreover, the neurotrophic role of CDCA was demonstrated by improving the low levels of BDNF in the presence of MPTP. The results of this study promise valuable insights into the potential therapeutic properties of CDCA in reducing the effects of PD and provide a basis for further research into bile acid-based treatments in neurodegenerative diseases.