Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation.
In humans, failure to express the fragile X mental retardation protein (FMRP) gives rise to fragile X syndrome, the most common form of inherited mental retardation. A fragile X knockout (fmr1 KO) mouse has been described that has some of the characteristics of patients with fragile X syndrome, including immature dendritic spines and subtle behavioral deficits. In our behavioral studies, fmr1 KO mice exhibited hyperactivity and a higher rate of entrance into the center of an open field compared with controls, suggesting decreased levels of anxiety. Our finding of impaired performance of fmr1 KO mice on a passive avoidance task is suggestive of a deficit in learning and memory. In an effort to understand what brain regions are involved in the behavioral abnormalities, we applied the [(14)C]deoxyglucose method for the determination of cerebral metabolic rates for glucose (CMR(glc)). We measured CMR(glc) in 38 regions in adult male fmr1 KO and WT littermates. We found CMR(glc) was higher in all 38 regions in fmr1 KO mice, and in 26 of the regions, differences were statistically significant. Differences in CMR(glc) ranged from 12% to 46%, and the greatest differences occurred in regions of the limbic system and primary sensory and posterior parietal cortical areas. Regions most affected are consistent with behavioral deficiencies and regions in which FMRP expression is highest. Higher CMR(glc) in fragile X mice may be a function of abnormalities found in dendritic spines.
Qin
Mei
M
Unit on Neurobiology, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD, USA.
Kang
Julia
J
Smith
Carolyn Beebe
CB
D000818:Animals; D001362:Avoidance Learning; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D003712:Dendrites / Q000502:physiology; D005106:Exploratory Behavior; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics; D008032:Limbic System / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009929:Organ Size; D010296:Parietal Lobe / Q000378:metabolism; D016601:RNA-Binding Proteins
D051860:Fragile X Messenger Ribonucleoprotein 1; D005947:Glucose; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497684:Fmr1 protein, mouse