Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation
Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation
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DOI：
10.1073/pnas.242377399
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发表时间：
2002-11-26
影响因子：
11.1
通讯作者：
Smith, CB
中科院分区：
文献类型：
--
作者：
Qin, M;Kang, J;Smith, CB
在人类中，脆性 X 智力低下蛋白 (FMRP) 的表达失败会导致脆性 X 综合征，这是遗传性智力低下最常见的形式。脆性 X 基因敲除 (fmr1 KO) 小鼠已被描述为具有脆性 X 综合征患者的一些特征，包括不成熟的树突棘和微妙的行为缺陷。在我们的行为研究中，与对照组相比，fmr1 KO 小鼠表现出过度活跃和进入开放区域中心的频率更高，这表明焦虑水平降低。我们发现 fmr1 KO 小鼠在被动回避任务中的表现受损，这表明学习和记忆存在缺陷。为了了解哪些大脑区域与行为异常有关，我们应用 [C-14] 脱氧葡萄糖方法来测定大脑葡萄糖代谢率 (CMRglc)。我们测量了成年雄性 fmr1 KO 和 WT 同窝小鼠 38 个区域的 CMRglc。我们发现 fmr1 KO 小鼠的所有 38 个区域中的 CMRglc 均较高，并且在其中 26 个区域中，差异具有统计学意义。 CMRglc 的差异范围为 12% 至 46%，最大差异发生在边缘系统区域以及初级感觉和后顶叶皮质区域。受影响最严重的区域与行为缺陷和 FMRP 表达最高的区域一致。脆弱 X 小鼠中较高的 CMRglc 可能是树突棘异常的结果。
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 [C-14]deoxyglucose method for the determination of cerebral metabolic rates for glucose (CMRglc). We measured CMRglc in 38 regions in adult male fmr1 KO and WT littermates. We found CMRglc, was higher in all 38 regions in fmr1 KO mice, and in 26 of the regions, differences were statistically significant. Differences in CMRglc 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 CMRglc in fragile X mice may be a function of abnormalities found in dendritic spines.