title: Reduced excitatory amino acid transporter 1 and metabotropic glutamate receptor 5 expression in the cerebellum of fragile X mental retardation gene 1 premutation carriers with fragile X-associated tremor/ataxia syndrome.
abstract: A premutation (PM) expansion (55-200 CGG) in the fragile X mental retardation gene 1 causes elevated messenger RNA and reduced fragile X mental retardation gene 1 protein. Young PM carriers can develop characteristic physical features and mild cognitive disabilities. In addition, individuals with PM, particularly male carriers, are at high risk to develop fragile X-associated tremor/ataxia syndrome (FXTAS) with aging. Human postmortem FXTAS brains show extensive white matter disease in the cerebellum and the presence of intranuclear inclusions throughout the brain, although their etiologic significance is unknown. In the current work, expression levels of the metabotropic glutamate (Glu) receptor 5 and the Glu transporter excitatory amino acid transporter 1, examined by reverse transcription polymerase chain reaction and western blot analyses, were found to be reduced in the postmortem cerebellum of PM carriers with FXTAS compared with age matched controls, with higher CGG repeat number having greater reductions in both proteins. These data suggests a dysregulation of Glu signaling in PM carriers, which would likely contribute to the development and severity of FXTAS.
authors: Department of Biochemistry and Molecular Medicine, University of California Davis, School of Medicine, Sacramento, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA, USA.
authors: Dalyir I
authors: DI
authors: Pretto
authors: Department of Biochemistry and Molecular Medicine, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors: Madhur
authors: M
authors: Kumar
authors: Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
authors: Zhengyu
authors: Z
authors: Cao
authors: Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, CA, USA.
authors: Christopher L
authors: CL
authors: Cunningham
authors: Department of Public Health Sciences, University of California Davis, School of Medicine, Davis, CA, USA.
authors: Blythe
authors: B
authors: Durbin-Johnson
authors: Department of Public Health Sciences, University of California Davis, School of Medicine, Davis, CA, USA.
authors: Lihong
authors: L
authors: Qi
authors: Department of Neurological Surgery, School of Medicine, University of California Davis, Davis, CA, USA.
authors: Robert
authors: R
authors: Berman
authors: Department of Pathology, School of Medicine, University of California Davis, Davis CA, USA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis School of Medicine, Sacramento, CA, USA.
authors: Stephen C
authors: SC
authors: Noctor
authors: Department of Pediatrics, School of Medicine, University of California Davis, Davis CA, USA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis School of Medicine, Sacramento, CA, USA.
authors: Randi J
authors: RJ
authors: Hagerman
authors: Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis School of Medicine, Sacramento, CA, USA.
authors: Isaac N
authors: IN
authors: Pessah
authors: Department of Biochemistry and Molecular Medicine, University of California Davis, School of Medicine, Sacramento, CA, USA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis School of Medicine, Sacramento, CA, USA. Electronic address: ftassone@ucdavis.edu.
authors: Flora
authors: F
authors: Tassone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001259:Ataxia / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000235:genetics; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics* / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics*; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome; D014202:Tremor / Q000235:genetics* / Q000473:pathology
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; C497683:FMR1 protein, human
keywords: EAAT1; EAAT2; FMR1; FMRP; FXTAS; Fragile X tremor/ataxia syndrome; Glu transporters; Premutation; mGluR5