Document Detail


Longitudinal in vivo developmental changes of metabolites in the hippocampus of Fmr1 knockout mice.
MedLine Citation:
PMID:  23046047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is studied in the Fmr1 knockout (KO) mouse, which models both the anatomical and behavioral changes observed in FXS patients. In vitro studies have shown many alterations in synaptic plasticity and increased density of immature dendritic spines in the hippocampus, a region involved in learning and memory. In this study, magnetic resonance imaging (MRI) and (1) H magnetic resonance spectroscopy (MRS) were used to determine in vivo longitudinal changes in volume and metabolites in the hippocampus during the critical period of early myelination and synaptogenesis at post-natal days (PND) 18, 21, and 30 in Fmr1 KO mice compared with wild-type (WT) controls. MRI demonstrated an increase in volume of the hippocampus in the Fmr1 KO mouse compared with controls. MRS revealed significant developmental changes in the ratios of hippocampal metabolites N-acetylaspartate (NAA), myo-inositol (Ins), and taurine to total creatine (tCr) in Fmr1 KO mice compared with WT controls. Ins was decreased at PND 30, and taurine was increased at all ages studied in Fmr1 KO mice compared with controls. An imbalance of brain metabolites in the hippocampus of Fmr1 KO mice during the critical developmental period of synaptogenesis and early myelination could have long-lasting effects that adversely affect brain development and contribute to ongoing alterations in brain function.
Authors:
Da Shi; Su Xu; Jaylyn Waddell; Susanna Scafidi; Steven Roys; Rao P Gullapalli; Mary C McKenna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-07
Journal Detail:
Title:  Journal of neurochemistry     Volume:  123     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-04     Completed Date:  2013-02-14     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  971-81     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Critical Period (Psychology)
Disease Models, Animal
Fragile X Mental Retardation Protein / genetics*,  metabolism
Fragile X Syndrome / genetics,  metabolism,  physiopathology
Hippocampus / growth & development*,  metabolism*,  physiopathology
Longitudinal Studies
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Myelin Sheath / physiology
Synapses / metabolism,  physiology
Grant Support
ID/Acronym/Agency:
K08 NS069815/NS/NINDS NIH HHS; NIH P01 HD016596/HD/NICHD NIH HHS; P01 HD016596/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Fmr1 protein, mouse; 139135-51-6/Fragile X Mental Retardation Protein
Comments/Corrections

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