Modulation of cognition and anxiety-like behavior by bone remodeling.
Modulation of cognition and anxiety-like behavior by bone remodeling.
复制标题
DOI：
10.1016/j.molmet.2017.10.001
复制
发表时间：
2017-12
影响因子：
8.1
通讯作者：
Karsenty G
中科院分区：
文献类型：
--
作者：
Khrimian L;Obri A;Karsenty G
骨源性激素骨钙素是促进正常大脑发育和功能所必需的，沿着最近描述的它在逆转衰老的认知表现方面的充分性，提出了新的问题。其中之一是评估随着年龄增长而迅速恶化的骨骼健康是否是认知和焦虑行为的重要决定因素。为了开始解决这个问题，我们使用了Runx 2单倍不足的小鼠，Runx 2是成骨细胞分化的主基因和骨钙素表达的主要调节因子。对照组和Runx 2 +/−组小鼠的大脑中骨钙素靶基因的表达和行为参数进行了评估，分别使用两种测定法进行认知和焦虑样行为。我们发现成年Runx 2 +/−小鼠骨吸收缺陷，生物活性骨钙素循环水平降低，骨钙素靶基因在大脑中的表达减少。因此，他们的认知功能明显受损，焦虑样行为增加。这些结果表明，骨重建是脑功能的决定因素。转录因子Runx 2决定循环骨钙素水平。Runx 2通过调节骨钙素表达影响认知。Runx 2还影响焦虑样行为。
That the bone-derived hormone osteocalcin is necessary to promote normal brain development and function, along with its recently described sufficiency in reversing cognitive manifestations of aging, raises novel questions. One of these is to assess whether bone health, which deteriorates rapidly with aging, is a significant determinant of cognition and anxiety-like behavior. To begin addressing this question, we used mice haploinsufficient for Runx2, the master gene of osteoblast differentiation and the main regulator of Osteocalcin expression. Control and Runx2+/− mice were evaluated for the expression of osteocalcin's target genes in the brain and for behavioral parameters, using two assays each for cognition and anxiety-like behavior. We found that adult Runx2+/− mice had defects in bone resorption, reduced circulating levels of bioactive osteocalcin, and reduced expression of osteocalcin's target genes in the brain. Consequently, they had significant impairment in cognitive function and increased anxiety-like behavior. These results indicate that bone remodeling is a determinant of brain function. The transcription factor Runx2 determines circulating osteocalcin levels. Runx2 influences cognition through its regulation of osteocalcin expression. Runx2 also influences anxiety-like behavior.
登录
查看更多内容
影响因子：
82.9
作者：
Nagahara AH;Merrill DA;Coppola G;Tsukada S;Schroeder BE;Shaked GM;Wang L;Blesch A;Kim A;Conner JM;Rockenstein E;Chao MV;Koo EH;Geschwind D;Masliah E;Chiba AA;Tuszynski MH
通讯作者：
Tuszynski MH
影响因子：
64.5
作者：
Oury F;Khrimian L;Denny CA;Gardin A;Chamouni A;Goeden N;Huang YY;Lee H;Srinivas P;Gao XB;Suyama S;Langer T;Mann JJ;Horvath TL;Bonnin A;Karsenty G
通讯作者：
Karsenty G
影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
64.8
作者：
Mosialou I;Shikhel S;Liu JM;Maurizi A;Luo N;He Z;Huang Y;Zong H;Friedman RA;Barasch J;Lanzano P;Deng L;Leibel RL;Rubin M;Nickolas T;Chung W;Zeltser LM;Williams KW;Pessin JE;Kousteni S
通讯作者：
Kousteni S
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J