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.
