Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.
Friederike KlempinValentina MosienkoSusann MatthesDaniel C VillelaMihail TodirasJosef M PenningerMichael BaderRobson A S SantosNatalia AleninaPublished in: Cellular and molecular life sciences : CMLS (2018)
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.
Keyphrases
- angiotensin converting enzyme
- angiotensin ii
- high intensity
- physical activity
- cerebral ischemia
- resting state
- white matter
- induced apoptosis
- cell proliferation
- high glucose
- cell cycle arrest
- spinal cord injury
- diabetic rats
- subarachnoid hemorrhage
- high fat diet induced
- cell cycle
- brain injury
- adipose tissue
- metabolic syndrome
- childhood cancer
- endoplasmic reticulum stress
- aortic dissection
- cell death
- endothelial cells
- depressive symptoms
- skeletal muscle
- binding protein
- anti inflammatory
- wild type