3 recherche sur le mot-clé 'Lactate'

Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study / Kathrin NICKEL ; Thomas LANGE ; Georg OELTZSCHNER ; Michael DACKO ; Dominique ENDRES ; Kimon RUNGE ; Anke SCHUMANN ; Katharina DOMSCHKE ; Michalis ROUSOS ; Ludger TEBARTZ VAN ELST in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 44 p. Titre : Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study Type de document : Texte imprimé et/ou numérique Auteurs : Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study [Texte imprimé et/ou numérique] / Kathrin NICKEL, Auteur ; Thomas LANGE, Auteur ; Georg OELTZSCHNER, Auteur ; Michael DACKO, Auteur ; Dominique ENDRES, Auteur ; Kimon RUNGE, Auteur ; Anke SCHUMANN, Auteur ; Katharina DOMSCHKE, Auteur ; Michalis ROUSOS, Auteur ; Ludger TEBARTZ VAN ELST, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 44 p. Mots-clés : Humans  Adult  *Autism Spectrum Disorder/diagnostic imaging/metabolism  Magnetic Resonance Spectroscopy/methods  Magnetic Resonance Imaging  Lactic Acid/metabolism  Biomarkers  Autism spectrum disorder  Lactate  Magnetic resonance spectroscopy  Mitochondria  Mitochondrial dysfunction  Posterior cingulate cortex  or travel grants within the last 3 years: Roche, Eli Lilly, Janssen-Cilag,  Novartis, Shire, UCB, GSK, Servier, Janssen, and Cyberonics. All other authors  declare that they do not have any conflicts of interest. Index. décimale : PER Périodiques Résumé : INTRODUCTION: Autism spectrum disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). MATERIALS AND METHODS: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. RESULTS: Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d=0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. LIMITATIONS: A cautious interpretation of our results is warranted due to a p value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. CONCLUSION: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function. En ligne : https://dx.doi.org/10.1186/s13229-023-00577-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

(1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome / Pooja Kri GUPTA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 31p. Titre : (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : 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 ((1)H-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. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome [Texte imprimé et/ou numérique] / Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 31p. Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : 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 ((1)H-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. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder / Neva M. CORRIGAN in Journal of Autism and Developmental Disorders, 42-1 (January 2012)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 42-1 (January 2012) . - p.105-115 Titre : Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Neva M. CORRIGAN, Auteur ; Dennis W.W. SHAW, Auteur ; Todd RICHARDS, Auteur ; Annette ESTES, Auteur ; Seth D. FRIEDMAN, Auteur ; Helen PETROPOULOS, Auteur ; Alan ARTRU, Auteur ; Stephen R. DAGER, Auteur Année de publication : 2012 Article en page(s) : p.105-115 Langues : Anglais (eng) Mots-clés : Autism  Developmental disorders  MRS  MRI  Mitochondrial disorders  Brain metabolism  Lactate Index. décimale : PER Périodiques Résumé : Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ( 1 HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3–4, 6–7 and 9–10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. 1 HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship. En ligne : http://dx.doi.org/10.1007/s10803-011-1216-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=151 [article] Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Neva M. CORRIGAN, Auteur ; Dennis W.W. SHAW, Auteur ; Todd RICHARDS, Auteur ; Annette ESTES, Auteur ; Seth D. FRIEDMAN, Auteur ; Helen PETROPOULOS, Auteur ; Alan ARTRU, Auteur ; Stephen R. DAGER, Auteur . - 2012 . - p.105-115. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 42-1 (January 2012) . - p.105-115 Mots-clés : Autism  Developmental disorders  MRS  MRI  Mitochondrial disorders  Brain metabolism  Lactate Index. décimale : PER Périodiques Résumé : Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ( 1 HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3–4, 6–7 and 9–10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. 1 HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship. En ligne : http://dx.doi.org/10.1007/s10803-011-1216-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=151