Brain and behavioural anomalies caused byTbx1haploinsufficiency are corrected by vitamin B12 DOI Creative Commons
Marianna Caterino, Debora Paris, Giulia Torromino

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 8(2), P. e202403075 - e202403075

Published: Nov. 20, 2024

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes brain metabolism might contribute to these phenotypes, as many of the deleted genes involved metabolic processes, but this unknown. This study shows for first time that Tbx1 haploinsufficiency causes imbalance. We studied two mouse models 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, transcriptomics. found +/− mice Df1/ + mice, with a multigenic includes , have elevated methylmalonic acid, which brain-toxic. Focusing on mutants, we they also more general metabolomic imbalance affects key pathways, such glutamine–glutamate fatty acid metabolism. provide transcriptomic evidence genotype–vitamin B12 treatment interaction. In addition, vitamin rescued behavioural anomaly mice. Further studies will be required establish whether specific metabolites affected by potential biomarkers disease status patients.

Language: Английский

Advances in Understanding Biomarkers and Treating Neurological Diseases -Role of the Cerebellar Dysfunction and Emerging Therapies DOI
Azhagu Madhavan Sivalingam

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102519 - 102519

Published: Sept. 1, 2024

Language: Английский

Citations

5
Exploring the Association Between Human Blood Metabolites and Autism Spectrum Disorder Risk: A Bidirectional Mendelian Randomization Study DOI Creative Commons
Wenhua Li, Suya Ma, Yulong Tian

et al.

Health Science Reports, Journal Year: 2025, Volume and Issue: 8(3)

Published: March 1, 2025

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with poorly understood etiology. Recent studies have suggested that metabolic dysregulation might be linked to the development of ASD; however, causal relationships remain unclear. This study aimed investigate association between these factors using two-sample Mendelian randomization (TSMR). We conducted TSMR analysis assess relationship blood metabolites and ASD summarized GWAS data. The metabolite dataset from Canadian Longitudinal Study Aging included 1091 309 ratios 7824 European individuals. data Psychiatric Genomics Consortium comprised 18,381 cases 27,969 controls. Blood were set as exposures outcome. primarily used inverse-variance weighted method, supplemented by MR-Egger, median, simple mode, mode methods. also sensitivity analyses confirm robustness. Replication, confounding, reserve performed verify causation. Additionally, pathway network pharmacology explore potential mechanisms. identified 55 known including 13 10 unknown associated ASD. our pathways, among which tryptophan metabolism was most notable (p = 0.0388). Gene Ontology functional Kyoto Encyclopedia Genes Genomes highlighted crucial such cellular glucuronidation, glucuronosyltransferase activity, bile secretion, significance apical part cell. Our findings indicate dodecenedioate, methionine sulfone, cysteine alanine ratio proline glutamate an impact on These results enhance understanding pathways involved in could lead new avenues for intervention prevention. Further research needed mechanisms underlying associations different populations.

Language: Английский

Citations

0
Tbx1 haploinsufficiency causes brain metabolic and behavioral anomalies in adult mice which are corrected by vitamin B12 treatment DOI Open Access
Marianna Caterino, Debora Paris, Giulia Torromino

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Abstract Introduction The brain-related phenotypes observed in 22q11.2 deletion syndrome (22q11.2DS) are highly variable and their origin is poorly understood. Changes brain metabolism may cause or contribute to the phenotypes, given that many of deleted genes (approx. 10%) implicated metabolic processes, but this currently unknown. It clearly important address knowledge gap, humans, primary material required for studying inaccessible. For reason, we sought issue using two mouse models 22q11.2DS. Methods We used three independent approaches investigate young adult mice, namely, mass spectrometry, nuclear magnetic resonance spectroscopy transcriptomics. selected study primarily Tbx1 single gene mutants because it candidate disease gene. then confirmed key findings multi-gene mutant Df1/+ . Results found have alterations specific metabolites, including methylmalonic acid, which brain-toxic, as well a more general metabolomic imbalance. provide transcriptomic evidence an interaction genotype-vB12 treatment, behavioural response vB12 rescued some anomaly mutants. conclude haploinsufficiency causes extensive anomalies, partially responsive treatment. suggest glutamine-glutamate fatty acid components phenotype these

Language: Английский

Citations

0
MICROBIOME-MODIFIED METABOLITES PREDICT ACUTE BRAIN INJURY OUTCOME DOI Creative Commons
Orlando DeLeon,

Hugo Dugolin Ceccato,

Ashley M. Sidebottom

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Abstract BACKGROUND Acute brain injury (ABI)-mediated disruption of the microbiome may potentiate inflammation and secondary (SBI). However, microbial-specific mediators mechanisms remain unclear. METHODS Thirty-five consecutive patients with ABI admitted to neuroscience critical care unit at University Chicago were prospectively studied. Injury severity hospital admission was assessed using Severity Score (ISS) Glasgow Coma Scale (GCS). Final neurologic function via Outcome extended (GOSe). Serum, plasma, stool targeted metabolomics, as well shotgun metagenomics, performed on longitudinal samples collected during hospitalization. RESULTS Multivariate analysis identified microbiome-modified metabolites that positively negatively associated functional outcomes after ABI. Novel identification conjugated bile acid (BA) species vitamin B12 precursors indicative outcome detected in first (within 48 hours). Network revealed greater integration across tissues tauro-α/μ-muricholic (TMCA) central cross-tissue metabolomes. CONCLUSIONS Microbiome be useful assessing inform treatment. Bile transformed by gut are predictive outcome.

Language: Английский

Citations

0
Brain and behavioural anomalies caused byTbx1haploinsufficiency are corrected by vitamin B12 DOI Creative Commons
Marianna Caterino, Debora Paris, Giulia Torromino

et al.

Life Science Alliance, Journal Year: 2024, Volume and Issue: 8(2), P. e202403075 - e202403075

Published: Nov. 20, 2024

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes brain metabolism might contribute to these phenotypes, as many of the deleted genes involved metabolic processes, but this unknown. This study shows for first time that Tbx1 haploinsufficiency causes imbalance. We studied two mouse models 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, transcriptomics. found +/− mice Df1/ + mice, with a multigenic includes , have elevated methylmalonic acid, which brain-toxic. Focusing on mutants, we they also more general metabolomic imbalance affects key pathways, such glutamine–glutamate fatty acid metabolism. provide transcriptomic evidence genotype–vitamin B12 treatment interaction. In addition, vitamin rescued behavioural anomaly mice. Further studies will be required establish whether specific metabolites affected by potential biomarkers disease status patients.

Language: Английский

Citations

0