Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency.
Animals
Autistic Disorder
/ drug therapy
Blood-Brain Barrier
Brain Diseases, Metabolic, Inborn
/ complications
Cerebrovascular Circulation
/ drug effects
Cognition Disorders
/ drug therapy
Creatine
/ deficiency
Creatinine
/ analogs & derivatives
Disease Models, Animal
Electroencephalography
Epilepsy
/ drug therapy
Hemodynamics
/ drug effects
Male
Mental Retardation, X-Linked
/ complications
Mice
Mice, Inbred C57BL
Phenotype
Plasma Membrane Neurotransmitter Transport Proteins
/ deficiency
Seizures
/ drug therapy
Stereotyped Behavior
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 10 2020
27 10 2020
Historique:
received:
20
07
2020
accepted:
25
09
2020
entrez:
28
10
2020
pubmed:
29
10
2020
medline:
27
2
2021
Statut:
epublish
Résumé
Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.
Identifiants
pubmed: 33110151
doi: 10.1038/s41598-020-75436-4
pii: 10.1038/s41598-020-75436-4
pmc: PMC7591530
doi:
Substances chimiques
Plasma Membrane Neurotransmitter Transport Proteins
0
cyclocreatine
6732XGX1RK
Creatinine
AYI8EX34EU
Creatine
MU72812GK0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18361Références
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