TY  - JOUR
AU  - Pons-Espinal, Meritxell
AU  - Gasperini, Caterina
AU  - Marzi, Matteo J
AU  - Braccia, Clarissa
AU  - Armirotti, Andrea
AU  - Pötzsch, Alexandra
AU  - Walker, Tara L
AU  - Fabel, Klaus
AU  - Nicassio, Francesco
AU  - Kempermann, Gerd
AU  - De Pietri Tonelli, Davide
TI  - MiR-135a-5p Is Critical for Exercise-Induced Adult Neurogenesis.
JO  - Stem cell reports
VL  - 12
IS  - 6
SN  - 2213-6711
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-07061
SP  - 1298-1312
PY  - 2019
AB  - Physical exercise stimulates adult hippocampal neurogenesis and is considered a relevant strategy for preventing age-related cognitive decline in humans. The underlying mechanisms remains controversial. Here, we show that exercise increases proliferation of neural precursor cells (NPCs) of the mouse dentate gyrus (DG) via downregulation of microRNA 135a-5p (miR-135a). MiR-135a inhibition stimulates NPC proliferation leading to increased neurogenesis, but not astrogliogenesis, in DG of resting mice, and intriguingly it re-activates NPC proliferation in aged mice. We identify 17 proteins (11 putative targets) modulated by miR-135 in NPCs. Of note, inositol 1,4,5-trisphosphate (IP3) receptor 1 and inositol polyphosphate-4-phosphatase type I are among the modulated proteins, suggesting that IP3 signaling may act downstream miR-135. miR-135 is the first noncoding RNA essential modulator of the brain's response to physical exercise. Prospectively, the miR-135-IP3 axis might represent a novel target of therapeutic intervention to prevent pathological brain aging.
KW  - Adult Stem Cells: metabolism
KW  - Aging: metabolism
KW  - Animals
KW  - Cell Proliferation
KW  - Gene Expression Regulation
KW  - Humans
KW  - Intercellular Signaling Peptides and Proteins: biosynthesis
KW  - Intracellular Signaling Peptides and Proteins: biosynthesis
KW  - Lateral Ventricles: cytology
KW  - Lateral Ventricles: metabolism
KW  - Mice
KW  - Mice, Knockout
KW  - MicroRNAs: biosynthesis
KW  - Neural Stem Cells: metabolism
KW  - Neurogenesis
KW  - Physical Conditioning, Animal
KW  - Stem Cell Niche
KW  - p38 Mitogen-Activated Protein Kinases: biosynthesis
LB  - PUB:(DE-HGF)16
C6  - pmid:31130358
C2  - pmc:PMC6565832
DO  - DOI:10.1016/j.stemcr.2019.04.020
UR  - https://pub.dzne.de/record/140739
ER  -