ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice

Jianping Wang, Xiaojie Fu, Di Zhang, Lie Yu, Nan Li, Zhengfang Lu, Yufeng Gao, Menghan Wang, Xi Liu, Chenguang Zhou, Wei Han, Bo Yan, Jian Wang

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated–neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-α, IFN-γ, or TGF-β on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke.

Original languageEnglish (US)
Pages (from-to)145-151
Number of pages7
JournalBehavioural Brain Research
Volume316
DOIs
StatePublished - Jan 1 2017

Keywords

  • ChAT+ neurons
  • Neurogenesis
  • Stroke
  • Subventricular zone

ASJC Scopus subject areas

  • Behavioral Neuroscience

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