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Transl Stroke Res. 2017 May 27. doi: 10.1007/s12975-017-0541-7. [Epub ahead of print]

Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone.

Author information

1
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. wjpwfy666@126.com.
2
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
3
Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450000, China.
4
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
5
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. jwang79@jhmi.edu.
6
Department of Human Anatomy, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450000, China. jwang79@jhmi.edu.
7
Department of Anesthesiology/Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. jwang79@jhmi.edu.

Abstract

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.

KEYWORDS:

Alpha-7 nicotinic acetylcholine receptor; ChAT-positive neuron; Neurogenesis; Subventricular zone

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