ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice.
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.
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Jianping
J
Wang
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Xiaojie
X
Fu
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Di
D
Zhang
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Lie
L
Yu
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Nan
N
Li
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Zhengfang
Z
Lu
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Yufeng
Y
Gao
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Menghan
M
Wang
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Xi
X
Liu
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Chenguang
C
Zhou
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Wei
W
Han
Department of Radiology, The Fourth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Bo
B
Yan
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.|Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Jian
J
Wang
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D020520:Brain Infarction / Q000209:etiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D000077265:Donepezil; D000089622:Doublecortin Domain Proteins; D007189:Indans / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D020547:Lateral Ventricles / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins; D018727:Muscarinic Antagonists / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009460:Neurologic Examination; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides; D010880:Piperidines / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
D002800:Cholinesterase Inhibitors; D000089622:Doublecortin Domain Proteins; D007189:Indans; D008869:Microtubule-Associated Proteins; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D010880:Piperidines; D011950:Receptors, Cholinergic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001285:Atropine; D000077265:Donepezil; D002795:Choline O-Acetyltransferase
ChAT+ neurons; Neurogenesis; Stroke; Subventricular zone