Abstract
Parkinson’s disease (PD) is a neurodegenerative disease associated with progressive impairment of motor and non-motor functions in aging people. Overwhelming evidence indicate that mitochondrial dysfunction is a central factor in PD pathophysiology, which impairs energy metabolism. While, several other studies have shown probiotic supplementations to improve host energy metabolism, alleviate the disease progression, prevent gut microbiota dysbiosis and alter commensal bacterial metabolites. But, whether probiotic and/or prebiotic supplementation can affect energy metabolism and cause the impediment of PD progression remains poorly characterized. Therefore, we investigated 8-weeks supplementation effects of probiotic [Lactobacillus salivarius subsp. salicinius AP-32 (AP-32)], residual medium (RM) obtained from the AP-32 culture medium, and combination of AP-32 and RM (A-RM) on unilateral 6-hydroxydopamine (6-OHDA)-induced PD rats. We found that AP-32, RM and A-RM supplementation induced neuroprotective effects on dopaminergic neurons along with improved motor functions in PD rats. These effects were accompanied by significant increases in mitochondrial activities in the brain and muscle, antioxidative enzymes level in serum, and altered SCFAs profile in fecal samples. Importantly, the AP-32 supplement restored muscle mass along with improved motor function in PD rats, and produced the best results among the supplements. Our results demonstrate that probiotic AP-32 and A-RM supplementations can recover energy metabolism via increasing SCFAs producing and mitochondria function. This restoring of mitochondrial function in the brain and muscles with improved energy metabolism might additionally be potentiated by ROS suppression by the elevated generation of antioxidants, and which finally leads to facilitated recovery of 6-OHDA-induced motor deficit. Taken together, this work demonstrates that probiotic AP-32 supplementation could be a potential candidate for alternate treatment strategy to avert PD progression.
Highlights
The Parkinson’s disease (PD) is a widespread neurodegenerative disease in aging individuals, marked by a gradual loss of dopaminergic neurons in the SNc pars compacta (SNc) region of the midbrain
There is no significant difference between untreated PD and L-DOPA-treated group
We found that the 8-week supplementation of probiotic [Lactobacillus salivarius subsp. salicinius AP-32 (AP32)], prebiotic [residual medium (RM)], and the symbiotic [combination of AP-32 and RM (A-RM)] significantly prevented dopaminergic neuron loss along with improved motor function in PD rats
Summary
The Parkinson’s disease (PD) is a widespread neurodegenerative disease in aging individuals, marked by a gradual loss of dopaminergic neurons in the SNc pars compacta (SNc) region of the midbrain. The gradual loss of dopaminergic neurons reduces dopamine turnover in the motor circuit of the brain leading to motor dysfunctions, such as bradykinesia, rigidity, tremor, and postural. Mitochondrial function is known to be disrupted in PD patients (Schapira et al, 1990). This disruption leads to decreased respiratory enzyme activity, decreased ATP production and energy failure (Verstreken et al, 2005). Mitochondrial damage with decrease of antioxidant defense capacity is imperative of net ROS production. There is an increase in oxidative stress resulting from the increased ROS production, and accumulation with simultaneous decrease in oxidative stress-related antioxidant enzymes. Augmenting the ATP deficit by stimulating glycolysis with pharmacological interventions has shown to attenuate PD progression (Cai et al, 2019)
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