Blackmore Daniel G, Steyn Frederik J, Carlisle Alison, O'Keeffe Imogen, Vien King-Year, Zhou Xiaoqing, Leiter Odette, Jhaveri Dhanisha, Vukovic Jana, Waters Michael J, Bartlett Perry F
Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4029, Australia.
iScience. 2021 Oct 14;24(11):103275. doi: 10.1016/j.isci.2021.103275. eCollection 2021 Nov 19.
Hippocampal function is critical for spatial and contextual learning, and its decline with age contributes to cognitive impairment. Exercise can improve hippocampal function, however, the amount of exercise and mechanisms mediating improvement remain largely unknown. Here, we show exercise reverses learning deficits in aged (24 months) female mice but only when it occurs for a specific duration, with longer or shorter periods proving ineffective. A spike in the levels of growth hormone (GH) and a corresponding increase in neurogenesis during this sweet spot mediate this effect because blocking GH receptor with a competitive antagonist or depleting newborn neurons abrogates the exercise-induced cognitive improvement. Moreover, raising GH levels with GH-releasing hormone agonist improved cognition in nonrunners. We show that GH stimulates neural precursors directly, indicating the link between raised GH and neurogenesis is the basis for the substantially improved learning in aged animals.
海马体功能对空间和情境学习至关重要，其随年龄衰退会导致认知障碍。运动可以改善海马体功能，然而，运动量以及介导改善的机制在很大程度上仍不清楚。在此，我们表明运动可逆转老年（24个月）雌性小鼠的学习缺陷，但前提是运动持续特定时长，更长或更短时间均无效。在此最佳时长期间，生长激素（GH）水平激增以及神经发生相应增加介导了这一效应，因为用竞争性拮抗剂阻断GH受体或耗尽新生神经元会消除运动诱导的认知改善。此外，用生长激素释放激素激动剂提高GH水平可改善不运动小鼠的认知。我们表明GH直接刺激神经前体细胞，这表明升高的GH与神经发生之间的联系是老年动物学习能力大幅改善的基础。
