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Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response

Item Type:Article
Title:Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response
Creators Name:Klempin, F. and Mosienko, V. and Matthes, S. and Villela, D.C. and Todiras, M. and Penninger, J.M. and Bader, M. and 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
Volume:75
Number:19
Page Range:3625-3634
Date:October 2018
Official Publication:https://doi.org/10.1007/s00018-018-2815-y
PubMed:View item in PubMed

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