title: Carnitine palmitoyltransferase 1C deficiency causes motor impairment and hypoactivity.
abstract: Carnitine palmitoyltransferase 1c (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions, but its only known functions to date are involved in the hypothalamic control of energy homeostasis and in hippocampus-dependent spatial learning. To identify other physiological and behavioral functions of this protein, we performed a battery of neurological tests on Cpt1c-deficient mice. The animals showed intact autonomic and sensory systems, but some motor disturbances were observed. A more detailed study of motor function revealed impaired coordination and gait, severe muscle weakness, and reduced daily locomotor activity. Analysis of motor function in these mice at ages of 6-24 weeks showed that motor disorders were already present in young animals and that impairment increased progressively with age. Analysis of CPT1C expression in different motor brain areas during development revealed that CPT1C levels were low from birth to postnatal day 10 and then rapidly increased peaking at postnatal day 21, which suggests that CPT1C plays a relevant role in motor function during and after weaning. As CPT1C is known to regulate ceramide levels, we measured these biolipids in different motor areas in adult mice. Cerebellar, striatum, and motor cortex extracts from Cpt1c knockout mice showed reduced levels of ceramide and its derivative sphingosine when compared to wild-type animals. Our results indicate that altered ceramide metabolism in motor brain areas induced by Cpt1c deficiency causes progressive motor dysfunction from a young age.
authors: Department of Basic Sciences, Facultat de Medicina i Ciències de la Salut, Universitat Internacional de Catalunya (UIC), 08195 Sant Cugat del Vallés, Spain; Centro de Investigación Biomédica en Red (CIBER)-Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
authors: Patricia
authors: P
authors: Carrasco
authors: Jordi
authors: J
authors: Jacas
authors: Ignasi
authors: I
authors: Sahún
authors: Helena
authors: H
authors: Muley
authors: Sara
authors: S
authors: Ramírez
authors: Beatriz
authors: B
authors: Puisac
authors: Pau
authors: P
authors: Mezquita
authors: Juan
authors: J
authors: Pié
authors: Mara
authors: M
authors: Dierssen
authors: Núria
authors: N
authors: Casals
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology*; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D018450:Disease Progression; D005684:Gait / Q000502:physiology; D008297:Male; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009069:Movement Disorders / Q000503:physiopathology*; D018908:Muscle Weakness / Q000503:physiopathology; D009460:Neurologic Examination; D012018:Reflex / Q000502:physiology; D045442:Rotarod Performance Test; D013110:Sphingosine / Q000378:metabolism
chemical_list: D002518:Ceramides; C558401:CPT1B protein, mouse; D002334:Carnitine O-Palmitoyltransferase; D013110:Sphingosine
keywords: CPT1; CPT1C; Ceramide; ER; KO; Locomotor activity; Motor coordination; Muscle strength; carnitine palmitoyltransferase 1; endoplasmic reticulum; knockout