A metabolomics approach to investigate urine levels of neurotransmitters and related metabolites in autistic children
| Autor: | Lello Zolla, Federica Gevi, Antonio Belardo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Autism Spectrum Disorder Synaptic Transmission Cresols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics Dopamine Internal medicine medicine Humans Vanillylmandelic acid Pyridoxal phosphate Child Neurotransmitter Molecular Biology METLIN Neurotransmitter Agents business.industry Homovanillic acid Glutamate receptor Brain Gastrointestinal Microbiome 030104 developmental biology Endocrinology chemistry Case-Control Studies Child Preschool Pyridoxal Phosphate Molecular Medicine Female business Metabolic Networks and Pathways 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1866:165859 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2020.165859 |
| Popis: | Since recently metabolic abnormalities in autistic children have been associated with ASD disturbs, the aim of this study is to determine the neurotransmitter levels in urine samples of autistic children and to analyse the altered metabolic pathway involved in their production. Thus, ASD-specific urinary metabolomic patterns were explored in 40 ASD children and 40 matched controls using untargeted metabolomics through UHPLC-mass spectrometry (Q-exactive analyser), and by using XCMS Metlin software for data interpretation. Through this new advanced technique, a more considerable number of urinary altered metabolites were recorded in autistic children, than in the previous investigations, which allowed us to collect metabolites involved in neurotransmitter production. In these subjects, a high amount of dopamine was revealed and an increased amount of homovanillic acid, to the detriment of noradrenaline and adrenaline production, as well as MHPG and vanillylmandelic acid, which were found lower. This indicates that the accumulation of dopamine is not due to its greater production, but its lesser biotransformation into noradrenaline, due to the blockage of the dopamine β-hydroxylase enzyme by 4-cresol and vitamin C, both found in high quantities in autistic subjects. Finally, a decreased amount of the active form of vitamin B6, pyridoxal phosphate (P5P), implicated in biotransformation of glutamate into γ-aminobutyric acid (GABA), was also detected, justifying the lower levels of latter. All of these alterations are correlated with a peculiar intestinal microbiome in autistic subjects, supporting the idea of a microbiota-gut-brain axis, then altered levels of neurotransmitters and altered neuronal transmission exist. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect