title: Etazolate abrogates the lipopolysaccharide (LPS)-induced downregulation of the cAMP/pCREB/BDNF signaling, neuroinflammatory response and depressive-like behavior in mice.
abstract: Increasing evidence has indicated that immune challenge by bacterial lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior remains unclear. Here using a model of depression induced by the repeated administration of LPS during 16days, and then investigated the influence of LPS on the expression of PDE4, interleukin-1β (IL-1β) and antidepressant action of etazolate in mice through forced swimming, novelty suppressed feeding, sucrose preference and open-field tests. Our results showed that etazolate pretreatment facilitated the recovery from weight loss and prevented the depressive-like behavior induced by repeated LPS administration. Moreover, the antidepressant action of etazolate was paralleled by significantly reducing the expression levels of PDE4A, PDE4B, PDE4D and IL-1β and up-regulating the cAMP/phosphorylated cAMP response-element binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus and prefrontal cortex of mice. These results indicate that the effects of etazolate on the depressive-like behavior induced by repeated LPS treatment may partially depend on the inhibition of PDE4 subtypes, the activation of the cAMP/pCREB/BDNF signaling and the anti-inflammatory responses in the hippocampus and prefrontal cortex.
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
authors.forename: P
authors.initials: P
authors.lastname: Lin
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. Electronic address: wangqinwen@nbu.edu.cn.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China. Electronic address: wangchuang@nbu.edu.cn.
authors.forename: C
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004974:Etazolate / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004974:Etazolate
keywords: cyclic adenosine monophosphate (cAMP); depression; etazolate; interleukin-1β (IL-1β); lipopolysaccharide (LPS); phosphodiesterase-4 (PDE4)