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| Item Type: | Article |
|---|---|
| Title: | Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response |
| Creators Name: | Klempin, F., Mosienko, V., Matthes, S., Villela, D.C., Todiras, M., Penninger, J.M., Bader, M., Santos, R.A.S. and Alenina, N. |
| Abstract: | Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism. |
| Keywords: | 5-HT, BrdU, Hippocampus, Physical Exercise, Neurobiology, Animals, Mice |
| Source: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-682X |
| Publisher: | Springer |
| Volume: | 75 |
| Number: | 19 |
| Page Range: | 3625-3634 |
| Date: | October 2018 |
| Additional Information: | Copyright © Springer International Publishing AG, part of Springer Nature 2018 |
| Official Publication: | https://doi.org/10.1007/s00018-018-2815-y |
| PubMed: | View item in PubMed |
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