Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease
Advances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In...
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| Format: | Article |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.621121/full |
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| author | Hassan Dakik Hassan Dakik Sarah Mantash Sarah Mantash Ali Nehme Ali Nehme Firas Kobeissy Masoud Zabet-Moghaddam Parvin Mirzaei Yehia Mechref Afsaneh Gaillard Laetitia Prestoz Kazem Zibara Kazem Zibara |
| author_facet | Hassan Dakik Hassan Dakik Sarah Mantash Sarah Mantash Ali Nehme Ali Nehme Firas Kobeissy Masoud Zabet-Moghaddam Parvin Mirzaei Yehia Mechref Afsaneh Gaillard Laetitia Prestoz Kazem Zibara Kazem Zibara |
| author_sort | Hassan Dakik |
| collection | DOAJ |
| description | Advances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In this study, we used liquid chromatography–tandem mass spectrometry and systems biology to identify differentially expressed proteins in a translational mouse model of PD after cell therapy. Proteins were extracted from five nigrostriatal-related brain regions of mice previously lesioned with 6-hydroxydopamine in the substantia nigra. Protein expression was compared in non-grafted brain to 1 and 7 days after intranigral grafting of E12.5 embryonic ventral mesencephalon (VM). We found a total of 277 deregulated proteins after transplantation, which are enriched for lipid metabolism, oxidative phosphorylation and PD, thus confirming that our animal model is similar to human PD and that the presence of grafted cells modulates the expression of these proteins. Notably, seven proteins (Acta1, Atp6v1e1, Eci3, Lypla2, Pip4k2a, Sccpdh, and Sh3gl2) were commonly down-regulated after engraftment in all studied brain regions. These proteins are known to be involved in the formation of lipids and recycling of dopamine (DA) vesicle at the synapse. Moreover, intranigral transplantation of VM cells decreased the expression of proteins related to oxidative stress, especially in the nigrostriatal pathway containing the DA grafted neurons. In the same regions, an up-regulation of several proteins including α-synuclein and tyrosine hydroxylase was observed, whereas expression of tetraspanin 7 was shut down. Overall, these results suggest that intranigral transplantation of VM tissue in an animal model of PD may induce a decrease of oxidative stress in the nigrostriatal pathway and a restoration of the machinery of neurotransmitters, particularly DA release to promote DA transmission through a decrease of D2 DA receptors endocytosis. Identification of new mechanistic elements involved in the nigrostriatal reconstruction process, using translational animal models and systems biology, is a promising approach to enhance the repair of this pathway in PD patients undergoing cell therapy. |
| first_indexed | 2024-12-17T02:06:56Z |
| format | Article |
| id | doaj.art-be0717d17595484d8f43dd912137ce00 |
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| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-17T02:06:56Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-be0717d17595484d8f43dd912137ce002022-12-21T22:07:40ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-03-011510.3389/fnins.2021.621121621121Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson DiseaseHassan Dakik0Hassan Dakik1Sarah Mantash2Sarah Mantash3Ali Nehme4Ali Nehme5Firas Kobeissy6Masoud Zabet-Moghaddam7Parvin Mirzaei8Yehia Mechref9Afsaneh Gaillard10Laetitia Prestoz11Kazem Zibara12Kazem Zibara13ER045, PRASE, Lebanese University, Beirut, LebanonUniversité de Tours, Tours, FranceER045, PRASE, Lebanese University, Beirut, LebanonINSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, Université de Poitiers, Poitiers, FranceER045, PRASE, Lebanese University, Beirut, LebanonMcGill University and Génome Québec Innovation Centre, McGill University, Montreal, QC, CanadaDepartment of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, LebanonCenter for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, United StatesCenter for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, United StatesCenter for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, United StatesINSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, Université de Poitiers, Poitiers, FranceINSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, Université de Poitiers, Poitiers, FranceER045, PRASE, Lebanese University, Beirut, LebanonDepartment of Biology, Faculty of Sciences-I, Lebanese University, Beirut, LebanonAdvances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In this study, we used liquid chromatography–tandem mass spectrometry and systems biology to identify differentially expressed proteins in a translational mouse model of PD after cell therapy. Proteins were extracted from five nigrostriatal-related brain regions of mice previously lesioned with 6-hydroxydopamine in the substantia nigra. Protein expression was compared in non-grafted brain to 1 and 7 days after intranigral grafting of E12.5 embryonic ventral mesencephalon (VM). We found a total of 277 deregulated proteins after transplantation, which are enriched for lipid metabolism, oxidative phosphorylation and PD, thus confirming that our animal model is similar to human PD and that the presence of grafted cells modulates the expression of these proteins. Notably, seven proteins (Acta1, Atp6v1e1, Eci3, Lypla2, Pip4k2a, Sccpdh, and Sh3gl2) were commonly down-regulated after engraftment in all studied brain regions. These proteins are known to be involved in the formation of lipids and recycling of dopamine (DA) vesicle at the synapse. Moreover, intranigral transplantation of VM cells decreased the expression of proteins related to oxidative stress, especially in the nigrostriatal pathway containing the DA grafted neurons. In the same regions, an up-regulation of several proteins including α-synuclein and tyrosine hydroxylase was observed, whereas expression of tetraspanin 7 was shut down. Overall, these results suggest that intranigral transplantation of VM tissue in an animal model of PD may induce a decrease of oxidative stress in the nigrostriatal pathway and a restoration of the machinery of neurotransmitters, particularly DA release to promote DA transmission through a decrease of D2 DA receptors endocytosis. Identification of new mechanistic elements involved in the nigrostriatal reconstruction process, using translational animal models and systems biology, is a promising approach to enhance the repair of this pathway in PD patients undergoing cell therapy.https://www.frontiersin.org/articles/10.3389/fnins.2021.621121/fullproteomecell therapynigrostriatal pathwaytransplantationParkinson diseasesystems biology |
| spellingShingle | Hassan Dakik Hassan Dakik Sarah Mantash Sarah Mantash Ali Nehme Ali Nehme Firas Kobeissy Masoud Zabet-Moghaddam Parvin Mirzaei Yehia Mechref Afsaneh Gaillard Laetitia Prestoz Kazem Zibara Kazem Zibara Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease Frontiers in Neuroscience proteome cell therapy nigrostriatal pathway transplantation Parkinson disease systems biology |
| title | Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease |
| title_full | Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease |
| title_fullStr | Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease |
| title_full_unstemmed | Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease |
| title_short | Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease |
| title_sort | analysis of the neuroproteome associated with cell therapy after intranigral grafting in a mouse model of parkinson disease |
| topic | proteome cell therapy nigrostriatal pathway transplantation Parkinson disease systems biology |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.621121/full |
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