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Longitudinal in vivo developmental changes of metabolites in the hippocampus of Fmr1 knockout mice
Author(s) -
Shi Da,
Xu Su,
Waddell Jaylyn,
Scafidi Susanna,
Roys Steven,
Gullapalli Rao P.,
McKenna Mary C.
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12048
Subject(s) - fmr1 , synaptogenesis , hippocampus , knockout mouse , endocrinology , fragile x syndrome , hippocampal formation , medicine , in vivo , biology , taurine , neuroscience , receptor , biochemistry , genetics , microbiology and biotechnology , fragile x , amino acid , gene
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 ( tC r) 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.