Creatine transporter-deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy
Duran-Trio L, Fernandes-Pires G, Grosse J, Soro-Arnaiz I, Roux-Petronelli C, Binz PA, De Bock K, Cudalbu C, Sandi C, Braissant O
Journal of inherited metabolic disease · 12 citas
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 independiente
- Gobierno
- National Science Foundation
- Gobierno
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Gobierno
- Swiss National Science Foundation
- Subvenciones
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (175778); Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A)
Según 3 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2021-12-22 · J Inherit Metab Dis · vol. 45 · número 2 · págs. 278–291
- Editorial
- Springer Science+Business Media
- Citado
- 19 citas · más que el 81% de estudios similares · 1.5× el promedio de su campo
- Referencias
- 64 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Muscle metabolism and nutrition · Muscle Physiology and Disorders · Genetic Neurodegenerative Diseases
- Palabras clave
- Creatine, Endocrinology, Internal medicine, Medicine, Atrophy, Muscle atrophy
- MeSH
- muscles, cerebellum, animals, humans, rats, cerebellar diseases, muscular atrophy, syndrome, creatine, membrane transport proteins, guanidinoacetate n-methyltransferase
10 autores
- Lara Durán-Trío🇨🇭 · autor de correspondenciaCentre Hospitalier Universitaire Vaudois; University of Lausanne
- Gabriella Fernandes‐Pires🇨🇭Centre Hospitalier Universitaire Vaudois; University of Lausanne
- Jocelyn Grosse🇨🇭École Polytechnique Fédérale de Lausanne
- Inés Soro-Arnáiz🇨🇭ETH Zurich; École Polytechnique Fédérale de Lausanne
- Clothilde Roux‐Petronelli🇨🇭Centre Hospitalier Universitaire Vaudois; University of Lausanne
- Pierre‐Alain Binz🇨🇭Centre Hospitalier Universitaire Vaudois; University of Lausanne
- Katrien De Bock🇨🇭ETH Zurich; École Polytechnique Fédérale de Lausanne
- Cristina Cudalbu🇨🇭Centre d'Imagerie BioMedicale; École Polytechnique Fédérale de Lausanne
- Carmen Sandi🇨🇭École Polytechnique Fédérale de Lausanne
- Olivier Braissant🇨🇭 · autor de correspondenciaCentre Hospitalier Universitaire Vaudois; University of Lausanne
Resumen
El texto original del estudio, en el idioma en que se publicó.
Creatine (Cr) is a nitrogenous organic acid and plays roles such as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes arginine:glycine amidinotransferase and guanidinoacetate methyltransferase, and specifically taken up by the transporter SLC6A8. Loss-of-function mutations in the genes encoding for the enzymes or the transporter cause creatine deficiency syndromes (CDS). CDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. Among CDS, the X-linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies, and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models, and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8Y389C knock-in rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency, and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co-occurred with both nervous and muscle dysfunctions, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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