TY - JOUR
T1 - Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone
AU - Wang, Jianping
AU - Lu, Zhengfang
AU - Fu, Xiaojie
AU - Zhang, Di
AU - Yu, Lie
AU - Li, Nan
AU - Gao, Yufeng
AU - Liu, Xianliang
AU - Yin, Chunmao
AU - Ke, Junji
AU - Li, Liyuan
AU - Zhai, Mengmeng
AU - Wu, Shiwen
AU - Fan, Jiahong
AU - Lv, Liang
AU - Liu, Junchao
AU - Chen, Xuemei
AU - Yang, Qingwu
AU - Wang, Jian
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (81571137, 81271284), the National Institutes of Health (R01NS078026, R01AT007317), and a "Stimulating and Advancing ACCM Research (StAAR)" grant from the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University. We thank Claire Levine for assistance with this manuscript. The authors assert no conflict of interest.
Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (81571137, 81271284), the National Institutes of Health (R01NS078026, R01AT007317), and a "Stimulating and Advancing ACCM Research (StAAR)" grant from the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University. We thank Claire Levine for assistance with this manuscript.
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Choline acetyltransferase-positive (ChAT+) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine. Mice subjected to MCAO exhibited elevated expression of cytomembrane and nuclear fibroblast growth factor receptor 1 (FGFR1), as well as increased expression of PI3K, pAkt, doublecortin (DCX), polysialylated - neuronal cell adhesion molecule (PSA-NCAM), and mammalian achaete-scute homolog 1 (Mash1). MCAO mice also had more glial fibrillary acidic protein (GFAP)/5-bromo-2′-deoxyuridine (BrdU)-positive cells and DCX-positive cells in the SVZ than did the sham-operated group. Methyllycaconitine treatment increased cytomembrane FGFR1 expression and GFAP/BrdU-positive cells, upregulated the levels of phosphoinositide 3-kinase (PI3K) and phospho-Akt (pAkt), decreased nuclear FGFR1 expression, decreased the number of DCX-positive cells, and reduced the levels of DCX, PSA-NCAM, and Mash1 in the SVZ of MCAO mice compared with levels in vehicle-treated MCAO mice. MCAO mice treated with α7 nAChR agonist PNU-282987 exhibited the opposite effects. Our data show that α7 nAChR may decrease the proliferation of neural stem cells and promote differentiation of existing neural stem cells after stroke. These results identify a new mechanism of SVZ ChAT+ neuron-induced neurogenesis.
AB - Choline acetyltransferase-positive (ChAT+) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine. Mice subjected to MCAO exhibited elevated expression of cytomembrane and nuclear fibroblast growth factor receptor 1 (FGFR1), as well as increased expression of PI3K, pAkt, doublecortin (DCX), polysialylated - neuronal cell adhesion molecule (PSA-NCAM), and mammalian achaete-scute homolog 1 (Mash1). MCAO mice also had more glial fibrillary acidic protein (GFAP)/5-bromo-2′-deoxyuridine (BrdU)-positive cells and DCX-positive cells in the SVZ than did the sham-operated group. Methyllycaconitine treatment increased cytomembrane FGFR1 expression and GFAP/BrdU-positive cells, upregulated the levels of phosphoinositide 3-kinase (PI3K) and phospho-Akt (pAkt), decreased nuclear FGFR1 expression, decreased the number of DCX-positive cells, and reduced the levels of DCX, PSA-NCAM, and Mash1 in the SVZ of MCAO mice compared with levels in vehicle-treated MCAO mice. MCAO mice treated with α7 nAChR agonist PNU-282987 exhibited the opposite effects. Our data show that α7 nAChR may decrease the proliferation of neural stem cells and promote differentiation of existing neural stem cells after stroke. These results identify a new mechanism of SVZ ChAT+ neuron-induced neurogenesis.
KW - Alpha-7 nicotinic acetylcholine receptor
KW - ChAT-positive neuron
KW - Neurogenesis
KW - Subventricular zone
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U2 - 10.1007/s12975-017-0541-7
DO - 10.1007/s12975-017-0541-7
M3 - Article
C2 - 28551702
AN - SCOPUS:85019664974
SN - 1868-4483
VL - 8
SP - 484
EP - 493
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 5
ER -