Systemic factors mediate exercise-induced enhancement of adult hippocampal neurogenesis
Abstract/Contents
- Abstract
- Aerobic exercise is widely considered to improve health and decrease risk of disease. Physically active humans have improved cognition later in life, and research in rodents has revealed that mice that voluntarily exercise on running wheels have increased adult hippocampal neurogenesis that is thought to support improved cognition. The mechanisms connecting physical activity with beneficial enhancement in adult hippocampal neurogenesis are poorly understood. With this dissertation work, we explored the systemic environment as a mediator of exercise-induced neurogenesis enhancement. We first established a paradigm of voluntary exercise that increased doublecortin+ new neuron production, dentate gyrus proliferation and long-term cell survival in 4-month old C57Bl/6 male mice. Then, we collected, pooled and intravenously transferred plasma from exercising mice to non-exercising mice in an attempt to recapitulate the effects of exercise on hippocampal neurogenesis. Excitingly, we show that immature neuron production, dentate gyrus proliferation and long-term cell survival are all increased by simply injecting a non-exercising mouse with plasma from a runner. We identified more than 2 dozen plasma proteins significantly increased or decreased with exercise. We tested 6 proteins, Interleukin 3, PDGF-AA, CXCL10, CCL1, CCL25 and PF4, for in vivo sufficiency to alter adult hippocampal neurogenesis. IL-3 was identified as a candidate protein capable of increasing the production of doublecortin+ cells, and IL-3 administration also increased proliferation in vivo and in vitro. Additionally, we explored the necessity of IL-3 for exercise-induced neurogenesis enhancement. To this end, we exercised mice deficient in IL-3. Without exercise, IL-3 KO mice have significantly diminished doublecortin+ cell production in the dentate gyrus. However, with voluntary exercise, IL-3 KO mice show significant increases in doublecortin+ cell production, proliferation and survival indicating that IL-3 is not necessary for exercise-induced neurogenesis. In summary, this works shows that exercise-induced increases in multiple neurogenesis parameters are at least partially mediated by systemic factors.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Betley, Michael |
|---|---|
| Associated with | Stanford University, Department of Neurosciences. |
| Primary advisor | Wyss-Coray, Anton |
| Thesis advisor | Wyss-Coray, Anton |
| Thesis advisor | Buckwalter, Marion |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Rando, Thomas A |
| Advisor | Buckwalter, Marion |
| Advisor | Monje-Deisseroth, Michelle |
| Advisor | Rando, Thomas A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Michael Betley. |
|---|---|
| Note | Submitted to the Department of Neurosciences. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Michael John Betley
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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