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 citas
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Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Animales
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2016-07-27 · Hum Mol Genet · vol. 25 · número 19 · págs. 4186–4200
- Editorial
- Oxford University Press
- Citado
- 55 citas · más que el 88% de estudios similares · 2.6× el promedio de su campo
- Referencias
- 61 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Muscle metabolism and nutrition · Pharmacological Effects and Toxicity Studies · Muscle Physiology and Disorders
- Palabras clave
- 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 autores
- Laura Baroncelli🇮🇹 · autor de correspondenciaIstituto di Scienza e Tecnologie dell'Informazione "Alessandro Faedo"; National Research Council
- Angelo Molinaro🇮🇹National Research Council; University of Florence
- Francesco Cacciante🇮🇹Scuola Normale Superiore
- M. Alessandri🇮🇹Fondazione Stella Maris; Istituti di Ricovero e Cura a Carattere Scientifico
- Debora Napoli🇮🇹Scuola Normale Superiore
- Elena Putignano🇮🇹National Research Council
- Jonida Tola🇮🇹National Research Council
- Vincenzo Leuzzi🇮🇹Sapienza University of Rome
- Giovanni Cioni🇮🇹University of Pisa; Fondazione Stella Maris; Istituti di Ricovero e Cura a Carattere Scientifico
- Tommaso Pizzorusso🇮🇹National Research Council; University of Florence
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
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