Department of Genetics and Development, Columbia University Medical Center, 701 W 168th St. Rm 1602, New York City, New York 10032, USA.
Institut Necker-Enfants Malades, CS 61431, Paris, France Institut National de la Santé et de la Recherche Médicale, U1151, F-75014 Paris, France Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
Nat Rev Endocrinol. 2018 Mar;14(3):174-182. doi: 10.1038/nrendo.2017.181. Epub 2018 Jan 29.
A remarkable, unexpected aspect of the bone-derived hormone osteocalcin is that it is necessary for both brain development and brain function in the mouse, as its absence results in a profound deficit in spatial learning and memory and an exacerbation of anxiety-like behaviour. The regulation of cognitive function by osteocalcin, together with the fact that its circulating levels decrease in midlife compared with adolescence in all species tested, raised the prospect that osteocalcin might be an anti-geronic hormone that could prevent age-related cognitive decline. As presented in this Review, recent data indicate that this is indeed the case and that osteocalcin is necessary for the anti-geronic activity recently ascribed to the plasma of young wild-type mice. The diversity and amplitude of the functions of osteocalcin in the brain, during development and postnatally, had long called for the identification of its receptor in the brain, which was also recently achieved. This Review presents our current understanding of the biology of osteocalcin in the brain, highlighting the bony vertebrate specificity of the regulation of cognitive function and pointing toward where therapeutic opportunities might exist.
令人惊讶的是，骨源性激素骨钙素的一个显著而意外的特点是，它对于老鼠的大脑发育和大脑功能都是必需的，因为其缺失会导致空间学习和记忆的严重缺陷，并加剧类似焦虑的行为。骨钙素对认知功能的调节，以及在所有测试物种中，其循环水平在中年时比青春期时降低的事实，提出了骨钙素可能是一种抗衰老激素，可以预防与年龄相关的认知能力下降的可能性。正如本综述所述，最近的数据表明，事实确实如此，骨钙素是最近归因于年轻野生型小鼠血浆的抗衰老活性所必需的。骨钙素在大脑中的发育和出生后的多样性和幅度的功能，长期以来一直要求确定其在大脑中的受体，最近也实现了这一目标。本综述介绍了我们目前对大脑中骨钙素生物学的理解，强调了认知功能调节的骨脊椎动物特异性，并指出了可能存在治疗机会的地方。
