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

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 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 GFAP/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 PI3K and 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.

Mechanisms of neuroprotection against ischemic insult by stress‐inducible phosphoprotein‐1/prion protein complex

“…) and ischemic stroke (Wang et al . ). Importantly, previous studies have shown that administration of α7nAChR agonists to humans is well tolerated (Deutsch et al .…”

“…), neurogenesis (Wang et al . ), and by activating neuroprotective signaling pathways (Dajas‐Bailador et al . ; Kihara et al .…”

Carbon monoxide-releasing molecule-3 protects against ischemic stroke by suppressing neuroinflammation and alleviating blood-brain barrier disruption

“…We sacrificed the mice on days 1 and 3 after tMCAO to determine the brain water content as previously described [ 30 , 37 ]. The brain was divided into two hemispheres from the anatomic midline.…”

“…We sacrificed mice on day 3 after surgery for immunofluorescence analysis as previously described [ 30 , 31 , 39 ]. Briefly, mice were anesthetized with an intraperitoneal injection of 5% chloral hydrate and perfused with PBS and 4% paraformaldehyde.…”

Nicotine is neuroprotective to neonatal neurons of sympathetic ganglion in rat

“…On the other hand, nicotine can protect cells against apoptosis through the upregulation of XIAP and survivin in a α3-nAChR-dependent manner (Dasgupta et al, 2006). Overall it appears that the cell proliferation and differentiation during development are mostly mediated by α7 nAChR and pro-survival effects are mediated by α3 or α4 nAChR (Dasgupta et al, 2006; Resende et al, 2008; 2008 a; Wang et al, 2017; West et al, 2003). These findings support our results indicating nicotine provides neuroprotection through both α3 and α7 nAChRs with a greater role for α3 nAChRs in preventing apoptosis upon NGF withdrawal in SCG neurons.…”