Objective/Rationale:
Inflammation contributes to the pathogenic process of Parkinson’s disease (PD). Increased numbers of anti-inflammatory regulatory T cells (Tregs) has been associated with inhibition of dopaminergic toxicity in pre-clinical models. Clostridium leptum bacterium in the colon can stimulate Treg expansion, which can inhibit inflammation. The objectives of this study are to determine whether oral feeding with Clostridium leptum can induce potent Treg responses and reduce toxicant-mediated toxicity of striatal dopamine system.
Project Description:
In this study, we will optimize the protocol for oral feeding with Clostridium leptum to enhance Treg responses in pre-clinical models. We will test both the effects of dose and duration of feeding of Clostridium leptum on increasing the numbers of Tregs in the spleen. Subsequently, we will use the optimized protocol for oral feeding with Clostridium leptum to test its neuroprotective effect on MPTP-induced striatal dopamine system toxicity by measuring the concentrations of dopamine and dopamine transporter in the striatum.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Given that Clostridium leptum is one of the components in the indigenous gut flora and is generally considered unharmful, our findings may aid in the design of new safe therapies for the treatment of PD.
Anticipated Outcome:
Positive findings will provide, for the first time, a proof of principle that oral feeding with Clostridium leptum induces Treg responses that may inhibit pathogenic processes that have been associated with PD.