TY - JOUR
T1 - An exercise “sweet spot” reverses cognitive deficits of aging by growth-hormone-induced neurogenesis
AU - Blackmore, Daniel G.
AU - Steyn, Frederik J.
AU - Carlisle, Alison
AU - O'Keeffe, Imogen
AU - Vien, King-Year
AU - Zhou, Xiaoqing
AU - Leiter, Odette
AU - Jhaveri, Dhanisha
AU - Vukovic, Jana
AU - Waters, Michael J.
AU - Bartlett, Perry F.
N1 - Funding Information:
This study was supported by the National Health and Medical Research Council Project Grants ( GNT1067909 and GNT1130141 to P.F.B. and D.B.) and from the Stafford Fox Medical Research Foundation (P.F.B.). O.L. received an Endeavor Research Fellowship from the Australian government. We thank the staff of the University of Queensland Biological Resources Facility for breeding and maintaining the animals in this study; Natalie Groves, Richard Wang, Tamara Koudijis, and Greg Robinson for technical assistance; Virginia Nink from the Queensland Brain Institute’s FACS Facility; Ashley Cooper, Rowan Tweedale, and Ann Turnley for editorial assistance; and Nick Valmas for assistance with illustrations. Imaging was performed at the Queensland Brain Institute's Advanced Microscopy Facility. Behavioral tests and surgery were performed at the Queensland Brain Institute's Behavior and Surgical Facility. The graphical abstract and Figure S10 were generated with BioRender.
Funding Information:
This study was supported by the National Health and Medical Research Council Project Grants (GNT1067909 and GNT1130141 to P.F.B. and D.B.) and from the Stafford Fox Medical Research Foundation (P.F.B.). O.L. received an Endeavor Research Fellowship from the Australian government. We thank the staff of the University of Queensland Biological Resources Facility for breeding and maintaining the animals in this study; Natalie Groves, Richard Wang, Tamara Koudijis, and Greg Robinson for technical assistance; Virginia Nink from the Queensland Brain Institute's FACS Facility; Ashley Cooper, Rowan Tweedale, and Ann Turnley for editorial assistance; and Nick Valmas for assistance with illustrations. Imaging was performed at the Queensland Brain Institute's Advanced Microscopy Facility. Behavioral tests and surgery were performed at the Queensland Brain Institute's Behavior and Surgical Facility. The graphical abstract and Figure S10 were generated with BioRender. D.B. F.S, A.C, I.O'K. K-Y.V. X.Z. O.L. D.J. and J.V. performed the experiments; M.W. provided reagents; D.B. and P.F.B. conceived the experiments, analyzed the data, and wrote the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/11/19
Y1 - 2021/11/19
N2 - 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.
AB - 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.
KW - Age
KW - Endocrine system physiology
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85119971347&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2021.103275
DO - 10.1016/j.isci.2021.103275
M3 - Article
C2 - 34761193
AN - SCOPUS:85119971347
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 11
M1 - 103275
ER -