1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome.
| Title: | 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. |
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| Authors: | Gupta, Pooja Kri1 (AUTHOR), Barak, Sharon2 (AUTHOR), Feuermann, Yonatan1 (AUTHOR), Goobes, Gil2 (AUTHOR), Kaphzan, Hanoch1 (AUTHOR) hkaphzan@univ.haifa.ac.il |
| Source: | Molecular Autism. 7/24/2024, Vol. 15 Issue 1, p1-14. 14p. |
| Subject Terms: | *ANGELMAN syndrome, *PROTON magnetic resonance, *METABOLOMICS, *LABORATORY mice, *METABOLOMIC fingerprinting |
| Abstract: | Background: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. Methods: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. Results: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. Limitations: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. Conclusions: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: <superscript>1</superscript>H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Gupta%2C+Pooja+Kri%22">Gupta, Pooja Kri</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Barak%2C+Sharon%22">Barak, Sharon</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Feuermann%2C+Yonatan%22">Feuermann, Yonatan</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Goobes%2C+Gil%22">Goobes, Gil</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kaphzan%2C+Hanoch%22">Kaphzan, Hanoch</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> hkaphzan@univ.haifa.ac.il</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Molecular+Autism%22">Molecular Autism</searchLink>. 7/24/2024, Vol. 15 Issue 1, p1-14. 14p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22ANGELMAN+syndrome%22">ANGELMAN syndrome</searchLink><br />*<searchLink fieldCode="DE" term="%22PROTON+magnetic+resonance%22">PROTON magnetic resonance</searchLink><br />*<searchLink fieldCode="DE" term="%22METABOLOMICS%22">METABOLOMICS</searchLink><br />*<searchLink fieldCode="DE" term="%22LABORATORY+mice%22">LABORATORY mice</searchLink><br />*<searchLink fieldCode="DE" term="%22METABOLOMIC+fingerprinting%22">METABOLOMIC fingerprinting</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. Methods: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. Results: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. Limitations: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. Conclusions: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Molecular Autism is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1186/s13229-024-00608-2 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 1 Subjects: – SubjectFull: ANGELMAN syndrome Type: general – SubjectFull: PROTON magnetic resonance Type: general – SubjectFull: METABOLOMICS Type: general – SubjectFull: LABORATORY mice Type: general – SubjectFull: METABOLOMIC fingerprinting Type: general Titles: – TitleFull: 1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Gupta, Pooja Kri – PersonEntity: Name: NameFull: Barak, Sharon – PersonEntity: Name: NameFull: Feuermann, Yonatan – PersonEntity: Name: NameFull: Goobes, Gil – PersonEntity: Name: NameFull: Kaphzan, Hanoch IsPartOfRelationships: – BibEntity: Dates: – D: 24 M: 07 Text: 7/24/2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 20402392 Numbering: – Type: volume Value: 15 – Type: issue Value: 1 Titles: – TitleFull: Molecular Autism Type: main |
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