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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Stem+Cells+Transl+Med
2017 ; 6
(6
): 1491-1503
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Angiotensin II Causes Apoptosis of Adult Hippocampal Neural Stem Cells and Memory
Impairment Through the Action on AMPK-PGC1? Signaling in Heart Failure
#MMPMID28244243
Kim MS
; Lee GH
; Kim YM
; Lee BW
; Nam HY
; Sim UC
; Choo SJ
; Yu SW
; Kim JJ
; Kim Kwon Y
; Who Kim S
Stem Cells Transl Med
2017[Jun]; 6
(6
): 1491-1503
PMID28244243
show ga
Data are limited on the mechanisms underlying memory impairment in heart failure
(HF). We hypothesized that angiotensin II (Ang II) may determine the fate of
adult hippocampal neural stem cells (HCNs), a cause of memory impairment in HF.
HCNs with neurogenesis potential were isolated and cultured from adult rat
hippocampi. Ang II decreased HCN proliferation in dose- and time-dependent
manners. Moreover, Ang II treatment (1 µM) for 48 hours induced apoptotic death,
which was attenuated by pretreatment with Ang II receptor blockers (ARBs). Ang II
increased mitochondrial reactive oxygen species (ROS) levels, which was related
to mitochondrial morphological changes and functional impairment. Moreover, ROS
activated the AMP-activated protein kinase (AMPK) and consequent peroxisome
proliferator-activated receptor gamma coactivator 1-alpha (PGC1?) expression,
causing cell apoptosis. In the HF rat model induced by left anterior descending
artery ligation, ARB ameliorated the spatial memory ability which decreased 10
weeks after ischemia. In addition, neuronal cell death, especially of newly born
mature neurons, was observed in HF rat hippocampi. ARB decreased cell death and
promoted the survival of newly born neural precursor cells and mature neurons. In
conclusion, Ang II caused HCN apoptosis through mitochondrial ROS formation and
subsequent AMPK-PGC1? signaling. ARB improved learning and memory behaviors
impaired by neuronal cell death in the HF animal model. These findings suggest
that HCN is one treatment target for memory impairment in HF and that ARBs have
additional benefits in HF combined with memory impairment. Stem Cells
Translational Medicine 2017;6:1491-1503.