Neurometabolite mapping highlights elevated myo-inositol profiles within the developing brain in down syndrome.

Autor: Patkee PA; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK., Baburamani AA; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK., Long KR; Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, SE1 1UL, UK., Dimitrova R; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK; Department of Forensic and Neurodevelopmental Science, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AB, UK., Ciarrusta J; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK; Department of Forensic and Neurodevelopmental Science, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AB, UK., Allsop J; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK., Hughes E; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK., Kangas J; Department of Forensic and Neurodevelopmental Science, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AB, UK., McAlonan GM; Department of Forensic and Neurodevelopmental Science, Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology and Neuroscience, King's College London, SE5 8AB, UK., Rutherford MA; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK., De Vita E; Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK; Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King's College London, St. Thomas' Hospital, London SE1 7EH, UK. Electronic address: Enrico.DeVita@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2021 Jun; Vol. 153, pp. 105316. Date of Electronic Publication: 2021 Mar 09.
DOI: 10.1016/j.nbd.2021.105316
Abstrakt: The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development. The aim of this study was to estimate mIns concentration levels and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr)] in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36-45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases. Relative to [Cho] and [Cr], we report elevated ratios of [mIns] in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios [Gly]/[Cr] and [Cho]/[Cr] also appear elevated. We observed elevated [mIns] in the ex vivo fetal cortical brain tissue in DS compared with controls. In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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