title: Interleukin-1β inhibits the differentiation of hippocampal neural precursor cells into serotonergic neurons.
abstract: Interleukin-1 beta (IL-1β) is one of pro-inflammatory cytokines. Recent studies have shown that IL-1β impairs hippocampal neurogenesis, mediates proliferation and differentiation of multipotent neural precursor cells (NPCs), and exerts effects of anti-proliferation, anti-neurogenesis, and pro-gliogenesis on embryonic hippocampal NPCs. The aim of this study was to examine the effect of IL-1β on the differentiation of hippocampal NPCs into functional serotonergic neurons, which play important roles in the pathophysiology and treatment of depression. Hippocampal NPCs were prepared from the hippocampus of neonatal rats (within 24h after birth). After three passages and phenotyping, hippocampal NPCs were cultured in a differentiating medium with various concentrations (5, 10, and 20 ng/mL) of IL-1β for 7 days. At the endpoint, the serotonergic differentiation of hippocampal NPCs in IL-1β-treated cultures decreased in a dose-dependent manner and this effect was blocked by IL-1ra, an IL-1 receptor antagonist capable of blocking the effects of IL-1 by binding to the same receptor (IL-1R1) without triggering signaling; serotonin in the lysate of the differentiated hippocampal NPCs decreased in IL-1β-treated cultures; and levels of Bcl-2 and phosphorylated extracellular-regulated kinase (pERK) were also lower in differentiated hippocampal NPCs with IL-1β treatment. These results support the hypothesis that IL-1β is an important factor in the stress-associated neuropathology and psychopathology and has relevance to the treatment of depressive symptoms in patients with depression.
authors.affiliation: Mental Health Center, Shantou University Medical College, Shantou 515065, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: Longlong
authors.initials: L
authors.lastname: Cao
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Li
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects* / Q000196:embryology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000187:drug effects*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D059326:Serotonergic Neurons / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D004396:Coloring Agents; D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D017472:Receptors, Interleukin-1; D013778:Tetrazolium Salts; D013844:Thiazoles; D012701:Serotonin; D048049:Extracellular Signal-Regulated MAP Kinases; C022616:thiazolyl blue