Alterations of Amino Acids and Monoamine Metabolism inMale Fmr1 Knockout Mice: A Putative Animal Model ofthe Human Fragile X Mental Retardation Syndrome

[摘要] The Fragile X syndrome, a common form ofmental retardation in humans, is caused bysilencing the fragile X mental retardation (FMR1)geneleading to the absence of the encoded fragileX mental retardation protein 1 (FMRP). Wedescribe morphological and behavioral abnormalitiesfor both affected humans and Fmr1knockout mice, a putative animal model for thehuman Fragile X syndrome. The aim of thepresent study was to identify possible neurochemicalabnormalities in Fmr1 knockout mice,with particular focus on neurotransmission.Significant region-specific differences: of basalneurotransmitter and metabolite levels werefound between wildtype and Fmr1 knockoutanimals, predominantly in juveniles (post-nataldays 28 to 31). Adults (postnatal days 209 to221) showed only few abnormalities as comparedwith the wildtype. In juvenile knockout mice,aspartate and taurine were especially increasedin cortical regions, striatum, hippocampus, cerebellum,and brainstem. In addition, juvenilesshowed an altered balance between excitatory andinhibitory amino acids in the caudal cortex,hippocampus, and brainstem. We detected veryfew differences in monoamine turnover in bothage stages. The results presented here providethe first evidence that lack of FMRP expressionin FMRP knockout mice is accompanied byage-dependent, region-specific alterations inneurotransmission.

[学科分类] 精神健康和精神病学