Parkinson’s disease (PD) is a common neurodegenerative disease, characterized by the loss of dopaminergic neurons and α-synuclein intracellular accumulation. Detrimental effects of PD involve inflammation, neurodegeneration and a reduced neurotrophic support1 . Moreover, PD can involve also the bidirectional interaction between the central nervous system and the enteric nervous system: the gut-brain axis2 . For this reason, gut microbiome modification plays a crucial role in the pathology of PD3 . The aim of this work was to study the effect of a probiotic formulation SLAB51 in in vitro and in vivo models of PD. For this aim, we first tested the probiotic formulation extract on differentiated SH-SY5Y into dopaminergic phenotype treated with 6-OHDA, to dissect, using western blotting analysis, the molecular pathways involved in neuroprotection and cell death. Then, we daily administered via oral gavage the probiotic formulation in 6- OHDA-lesioned C57BL/6 mice to evaluate the effects of the probiotic on behavior, neurodegeneration and inflammation. Our in vitro studies indicated that SLAB51 extract was able to modulate the BNDF pathway, increasing neuroprotective protein levels and decreasing the levels of neuronal death proteins. Thus, we investigated the probiotic effects in vivo using apomorphine test, EBS test and cylinder test. Interestingly, SLAB51 was able to counteract the detrimental effects of 6-OHDA. Moreover, basing on the immunohistochemistry and immunofluorescence studies we observed a decrease in dopaminergic loss, inflammation and gliosis induced by 6-OHDA in both substantia nigra and striatum in SLAB51-treated mice. Notably, in this study we observed in both the models an involvement of PPARγ that may trigger anti-inflammatory and antioxidant activities as well as a modulation of pro-survival pathways. Overall, our studies suggested that SLAB51 can represent a promising candidate for PD adjuvant therapy confirming previous evidence on the effect of gut microbiota modulation on neuroprotective pathways4.

EFFECTS OF THE PROBIOTIC FORMULATION SLAB51 IN IN VITRO AND IN VIVO MODELS OF PARKINSON’S DISEASE

Margherita Alfonsetti;Giorgia Lombardozzi;Michele d’Angelo;
2022-01-01

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease, characterized by the loss of dopaminergic neurons and α-synuclein intracellular accumulation. Detrimental effects of PD involve inflammation, neurodegeneration and a reduced neurotrophic support1 . Moreover, PD can involve also the bidirectional interaction between the central nervous system and the enteric nervous system: the gut-brain axis2 . For this reason, gut microbiome modification plays a crucial role in the pathology of PD3 . The aim of this work was to study the effect of a probiotic formulation SLAB51 in in vitro and in vivo models of PD. For this aim, we first tested the probiotic formulation extract on differentiated SH-SY5Y into dopaminergic phenotype treated with 6-OHDA, to dissect, using western blotting analysis, the molecular pathways involved in neuroprotection and cell death. Then, we daily administered via oral gavage the probiotic formulation in 6- OHDA-lesioned C57BL/6 mice to evaluate the effects of the probiotic on behavior, neurodegeneration and inflammation. Our in vitro studies indicated that SLAB51 extract was able to modulate the BNDF pathway, increasing neuroprotective protein levels and decreasing the levels of neuronal death proteins. Thus, we investigated the probiotic effects in vivo using apomorphine test, EBS test and cylinder test. Interestingly, SLAB51 was able to counteract the detrimental effects of 6-OHDA. Moreover, basing on the immunohistochemistry and immunofluorescence studies we observed a decrease in dopaminergic loss, inflammation and gliosis induced by 6-OHDA in both substantia nigra and striatum in SLAB51-treated mice. Notably, in this study we observed in both the models an involvement of PPARγ that may trigger anti-inflammatory and antioxidant activities as well as a modulation of pro-survival pathways. Overall, our studies suggested that SLAB51 can represent a promising candidate for PD adjuvant therapy confirming previous evidence on the effect of gut microbiota modulation on neuroprotective pathways4.
2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11575/137980
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