Oral sodium butyrate alleviates motor deficits and dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson’s disease rat model
Short-chain fatty acids regulate intestinal homeostasis and modulate the gut–brain axis, suggesting they may be applicable in adjunctive treatments for Parkinson’s disease (PD). However, the therapeutic efficacy of sodium butyrate (NaB) in PD remains unclear. Using appropriate PD animal models may aid in clarifying the therapeutic effects of NaB and facilitate the development of NaB-based PD treatment strategies. We comprehensively evaluated the therapeutic effects of oral NaB in rats with 6-hydroxydopamine (6-OHDA)-induced PD. We induced hemiparkinsonism in rats by administering unilateral 6-OHDA in the medial forebrain bundle. At 24 h after confirming lesion development, some rats were randomized to receive oral NaB (administered daily) over 4 weeks. Behavioral assessments—comprising gait analysis, open-field activity, and apomorphine-induced rotations—were performed longitudinally in weeks 1 and 4. Finally, dopaminergic neuronal degeneration was evaluated to correlate functional recovery with structural neuroprotection. The 4-week oral NaB intervention significantly alleviated 6-OHDA-induced motor deficits (i.e., locomotor activity, akinesia, and gait) and anxiety-like behavior; however, it did not alleviate apomorphine-induced rotations. Tyrosine hydroxylase immunohistochemical staining confirmed these findings, indicating that the dopaminergic neuron survival rate was significantly higher in the NaB-treated groups than in the sham control group. Early long-term oral NaB treatment afforded neuroprotection and alleviated motor and non-motor deficits (such as gait and central time in the open field) in rats with 6-OHDA-induced PD. Our model indicates the therapeutic potential of oral NaB and provides a translational framework for investigating the mechanisms of NaB therapy in PD and associated neurological disorders.