Novel translational phenotypes and biomarkers for creatine transporter deficiency.
EEG
biomarkers
creatine transporter deficiency
epilepsy
optical imaging
Journal
Brain communications
ISSN: 2632-1297
Titre abrégé: Brain Commun
Pays: England
ID NLM: 101755125
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
03
2020
revised:
20
05
2020
accepted:
10
06
2020
entrez:
21
9
2020
pubmed:
22
9
2020
medline:
22
9
2020
Statut:
epublish
Résumé
Creatine transporter deficiency is a metabolic disorder characterized by intellectual disability, autistic-like behaviour and epilepsy. There is currently no cure for creatine transporter deficiency, and reliable biomarkers of translational value for monitoring disease progression and response to therapeutics are sorely lacking. Here, we found that mice lacking functional creatine transporter display a significant alteration of neural oscillations in the EEG and a severe epileptic phenotype that are recapitulated in patients with creatine transporter deficiency. In-depth examination of knockout mice for creatine transporter also revealed that a decrease in EEG theta power is predictive of the manifestation of spontaneous seizures, a frequency that is similarly affected in patients compared to healthy controls. In addition, knockout mice have a highly specific increase in haemodynamic responses in the cerebral cortex following sensory stimuli. Principal component and Random Forest analyses highlighted that these functional variables exhibit a high performance in discriminating between pathological and healthy phenotype. Overall, our findings identify novel, translational and non-invasive biomarkers for the analysis of brain function in creatine transporter deficiency, providing a very reliable protocol to longitudinally monitor the efficacy of potential therapeutic strategies in preclinical, and possibly clinical, studies.
Identifiants
pubmed: 32954336
doi: 10.1093/braincomms/fcaa089
pii: fcaa089
pmc: PMC7472907
doi:
Types de publication
Journal Article
Langues
eng
Pagination
fcaa089Informations de copyright
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.
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