Etanercept ameliorates chronic mild stress-induced depressive-like behavior in rats: Crosstalk between MAPK and STAT3 pathways and norepinephrine and serotonin transporters.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: 2005- : Amsterdam : Elsevier Science
      Original Publication: Amsterdam, North Holland Pub. Co.
    • Subject Terms:
      Etanercept*/pharmacology ; Etanercept*/therapeutic use ; Rats, Wistar* ; Depression*/drug therapy ; Depression*/metabolism ; Stress, Psychological*/drug therapy ; Stress, Psychological*/metabolism ; Stress, Psychological*/psychology ; STAT3 Transcription Factor*/metabolism ; Behavior, Animal*/drug effects ; Antidepressive Agents*/pharmacology ; Antidepressive Agents*/therapeutic use ; Serotonin Plasma Membrane Transport Proteins*/metabolism; Animals ; Male ; Rats ; Norepinephrine Plasma Membrane Transport Proteins/metabolism ; Norepinephrine/metabolism ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/drug effects ; Fluoxetine/pharmacology ; Fluoxetine/therapeutic use ; MAP Kinase Signaling System/drug effects ; Serotonin/metabolism ; Chronic Disease ; Signal Transduction/drug effects
    • Abstract:
      Depression is a serious medical illness characterized by persistent feelings of sadness, hopelessness, and lack of interest in daily activities. It can interfere with daily functioning and quality of life. Despite decades of research, the pathophysiology of depression remains incompletely understood. The correlation between depression and inflammation has recently attracted considerable attention. This study investigated the potential antidepressant effect of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, utilizing a chronic mild stress (CMS) model in rats. Male Wistar rats were divided into two groups; one following a non-stressed protocol and the other a stressed protocol for 5 weeks. From the beginning of the third week, rats were treated either with saline daily or with etanercept twice a week (0.3 mg/kg, i.p.) or with fluoxetine daily (10 mg/kg, i.p) as a reference. Etanercept exhibited comparable effects to those of fluoxetine in counteracting CMS-induced behavioral manifestation in the forced swimming and splash tests. Etanercept also restored serotonin and norepinephrine levels to control values in the prefrontal cortex (PFC). Moreover, the current study verified the antioxidant and anti-inflammatory effects of etanercept. Interestingly, etanercept halted the expression of both norepinephrine and serotonin transporters in stressed rats. This could be attributed to abrogation of the p38 mitogen-activated protein kinase (p38 MAPK) and signal transducer and activator of transcription 3 (STAT-3) pathways in the PFC. The findings of the present study contribute to the understanding of the potential of etanercept as an antidepressant and provide insights into the neurobiological mechanisms underlying its therapeutic effects.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Chronic mild stress; Depression; Etanercept; Neuroinflammation; Norepinephrine transporter; Serotonin transporter
    • Accession Number:
      OP401G7OJC (Etanercept)
      0 (STAT3 Transcription Factor)
      0 (Antidepressive Agents)
      0 (Serotonin Plasma Membrane Transport Proteins)
      0 (Norepinephrine Plasma Membrane Transport Proteins)
      X4W3ENH1CV (Norepinephrine)
      01K63SUP8D (Fluoxetine)
      333DO1RDJY (Serotonin)
      0 (Stat3 protein, rat)
    • Publication Date:
      Date Created: 20240630 Date Completed: 20240724 Latest Revision: 20240828
    • Publication Date:
      20240828
    • Accession Number:
      10.1016/j.ejphar.2024.176801
    • Accession Number:
      38945285