A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging
Baroncelli L, Molinaro A, Cacciante F, Alessandrì MG, Napoli D, Putignano E, Tola J, Leuzzi V, Cioni G, Pizzorusso T
Human molecular genetics · 40 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Funding not disclosed
Publication
- Published
- 2016-07-27 · Hum Mol Genet · vol. 25 · issue 19 · pp. 4186–4200
- Publisher
- Oxford University Press
- Cited
- 55 citations · more than 88% of similar papers · 2.6× the field average
- References
- 61 works
- Access
- Free to read
- Research areas
- Muscle metabolism and nutrition · Pharmacological Effects and Toxicity Studies · Muscle Physiology and Disorders
- Keywords
- Neuropathology, Neuroscience, Cognitive decline, Intellectual disability, Hippocampal formation, Biology, Epilepsy, Neurogenesis, Dementia, Internal medicine, Disease, Medicine, Genetics
- MeSH
- brain, animals, mice, transgenic, humans, mice, brain diseases, metabolic, inborn, disease models, animal, creatine, membrane transport proteins, aging, plasma membrane neurotransmitter transport proteins, intellectual disability, cognitive dysfunction, x-linked intellectual disability
10 authors
From IT
- Laura Baroncelli · correspondingIstituto di Scienza e Tecnologie dell'Informazione "Alessandro Faedo"; National Research Council
- Angelo MolinaroNational Research Council; University of Florence
- Francesco CaccianteScuola Normale Superiore
- M. AlessandriFondazione Stella Maris; Istituti di Ricovero e Cura a Carattere Scientifico
- Debora NapoliScuola Normale Superiore
- Elena PutignanoNational Research Council
Abstract
Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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