Document Detail

Altered cerebral protein synthesis in fragile X syndrome: studies in human subjects and knockout mice.
MedLine Citation:
PMID:  23299245     Owner:  NLM     Status:  MEDLINE    
Dysregulated protein synthesis is thought to be a core phenotype of fragile X syndrome (FXS). In a mouse model (Fmr1 knockout (KO)) of FXS, rates of cerebral protein synthesis (rCPS) are increased in selective brain regions. We hypothesized that rCPS are also increased in FXS subjects. We measured rCPS with the L-[1-(11)C]leucine positron emission tomography (PET) method in whole brain and 10 regions in 15 FXS subjects who, because of their impairments, were studied under deep sedation with propofol. We compared results with those of 12 age-matched controls studied both awake and sedated. In controls, we found no differences in rCPS between awake and propofol sedation. Contrary to our hypothesis, FXS subjects under propofol sedation had reduced rCPS in whole brain, cerebellum, and cortex compared with sedated controls. To investigate whether propofol could have a disparate effect in FXS subjects masking usually elevated rCPS, we measured rCPS in C57Bl/6 wild-type (WT) and KO mice awake or under propofol sedation. Propofol decreased rCPS substantially in most regions examined in KO mice, but in WT mice caused few discrete changes. Propofol acts by decreasing neuronal activity either directly or by increasing inhibitory synaptic activity. Our results suggest that changes in synaptic signaling can correct increased rCPS in FXS.
Mei Qin; Kathleen C Schmidt; Alan J Zametkin; Shrinivas Bishu; Lisa M Horowitz; Thomas V Burlin; Zengyan Xia; Tianjiang Huang; Zenaide M Quezado; Carolyn Beebe Smith
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2013-01-09
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-507     Citation Subset:  IM    
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MeSH Terms
Brain / metabolism*,  radiography
Fragile X Mental Retardation Protein / genetics
Fragile X Syndrome / genetics,  metabolism*,  radiography
Hypnotics and Sedatives / administration & dosage
Mice, Knockout
Positron-Emission Tomography
Propofol / administration & dosage
Protein Biosynthesis*
Synapses / genetics,  metabolism
Synaptic Transmission / drug effects,  genetics
Reg. No./Substance:
0/Fmr1 protein, mouse; 0/Hypnotics and Sedatives; 139135-51-6/Fragile X Mental Retardation Protein; YI7VU623SF/Propofol

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