title: Nicotine contributes to the neural stem cells fate against toxicity of microglial-derived factors induced by Aβ via the Wnt/β-catenin pathway.
abstract: Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of β-amyloid peptide (Aβ). The viability, proliferation, differentiation, apoptosis of NSCs and underlying mechanisms associated with Wnt signaling pathway were investigated. The results showed that Aβ could directly damage NSCs. Furthermore, concomitant to elevated levels of TNF-α, IL-1β derived from microglias, the NSCs had been damaged more severely with the upregulation of Axin 2, p-β-catenin and the downregulation of β-catenin, p-GSK-3β, microtubule-associated protein-2, choline acetyltransferase. However, addition of 10 μmol/L nicotine before microglias treated with Aβ was beneficial to protect the NSCs against neurotoxicity of microglial-derived factors induced by Aβ, which partially rescued proliferation, differentiation and inhibited apoptosis of NSCs via activation of Wnt/β-catenin pathway. Taken together, these data imply that low concentration nicotine attenuates NSCs injury induced by microglial-derived factors via Wnt signaling pathway. Thus, treatment with nicotinic acetylcholine receptor agonist provides a promising research field for neural stem cell fate and therapeutic intervention in neuroinflammation diseases.
authors.affiliation: a Department of Pharmacy , Zhujiang Hospital of Southern Medical University , Guangzhou , China.|b Department of Biopharmaceutical , Yulin Normal University , Yulin , China.
authors.forename: De-Qi
authors.initials: DQ
authors.lastname: Jiang
authors.affiliation: c Department of Pharmacy , the Third Affiliated Hospital of Southern Medical University , Guangzhou , China.
authors.forename: Mei-Dan
authors.initials: MD
authors.lastname: Wei
authors.affiliation: d Department of Neurosurgery , Nanfang Hospital of Southern Medical University , Guangzhou , China.
authors.forename: Ke-Wan
authors.initials: KW
authors.lastname: Wang
authors.affiliation: a Department of Pharmacy , Zhujiang Hospital of Southern Medical University , Guangzhou , China.
authors.forename: Yan-Xian
authors.initials: YX
authors.lastname: Lan
authors.affiliation: a Department of Pharmacy , Zhujiang Hospital of Southern Medical University , Guangzhou , China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhu
authors.affiliation: a Department of Pharmacy , Zhujiang Hospital of Southern Medical University , Guangzhou , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051153:Wnt Proteins; D051176:beta Catenin; D009538:Nicotine
keywords: alzheimer's disease; neural stem cell; nicotine; α7-nAChR; β-catenin