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[Q. Neuroscience-33]



                Oral administration of Proteus mirabilis, a gut bacterium


                  linked to Parkinson’s disease, alters the expression of a


                                neurotrophin in the intestine of mice



          Jun Heyok Kwak¹˙², Miran Jeong¹˙²˙³, Jin Gyu Choi¹˙²˙³, Eugene Huh⁴, Jae-Won Lee², Im-Ho Lee², Dong-

                                 Hyun Kim¹˙²˙³, Myung Sook Oh¹˙²˙³, Jung-Hye Choi¹˙²˙³˙*


          ¹Neurobiota Research Center (NRC), Kyung Hee University, Seoul 02447, South Korea, ²Department of Life and

         Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, South Korea, ³College of Pharmacy, Kyung Hee
           University, Seoul 02447, South Korea, ⁴Medical Science of Meridian, Graduate School, , Kyung Hee University,
                                                 Seoul 02447, South Korea





        Emerging studies suggest that gut dysbiosis play a critical role in several neurological disorders including Parkinson’s
        disease (PD). However, how gut microbiota can affect the function of the nervous system remain largely unknown.

        Previously, a gut bacterium Proteus mirabilis has been demonstrated to induce PD symptoms in mice. In this study,
        we aimed to investigate the effect of P. mirabilis on the expression of four neurotrophins (neurotrophin A-D) in the

        intestine. Oral administration of P. mirabilis inhibited the mRNA expression of neurotrophin D, but not the protein
        expression of that. In contrast, both mRNA and protein expression of neurotrophin A was significantly reduced in

        the colon of mice with oral administration of P. mirabilis. Notably, the reduced levels of neurotrophin A were also
        observed in the intestine of neurotoxin-induced PD mice. Tyndallized P. mirabilis (PM-T) inhibited the expression of

        neurotrophin  A  in  both  enteric  epithelial  cells  and  neuronal  cells.  In  enteric  epithelial  cells,  PM-T  significantly
        suppressed the phosphorylation of CREB while PM-T reduced that of NF-kB in neuronal cells. Taken together, these
        data suggest that P. mirabilis may inhibit the expression of neurotrophin A in the epithelial and/or neuronal cells of

        the colon.
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