A Selective Nuclear Factor-κB Inhibitor, JSH-23, Exhibits Antidepressant-like Effects and Reduces Brain Inflammation in Rats

Autor: Ahmad Nassar, Jacob Kaplanski, Abed N. Azab
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Pharmaceuticals, Vol 17, Iss 10, p 1271 (2024)
Druh dokumentu: article
ISSN: 17101271
1424-8247
DOI: 10.3390/ph17101271
Popis: Background: Accumulating evidence suggests that nuclear factor (NF)-κB is involved in the pathophysiology of mood disorders. Objectives and Methods: We conducted two experimental protocols in rats to investigate the effects of a selective NF-κB inhibitor (JSH-23) on (i) lipopolysaccharide (LPS)-induced inflammation and (ii) on behavioral phenotypes in rat models of depression (sucrose consumption test and forced swim test) and mania (amphetamine-induced hyperactivity test). Additionally, we tested the effects of JSH-23 on levels of inflammatory components (interleukin-6, prostaglandin E2, nuclear phospho-p65, and tumor necrosis factor-α) in the brain. Results: Acute treatment with JSH-23 (10 mg/kg, intraperitoneally [ip]) led to potent anti-inflammatory effects in LPS-treated rats, including a diminished hypothermic response to LPS and a reduction in pro-inflammatory mediators’ levels in the brain. Chronic treatment with JSH-23 (3 mg/kg, ip, once daily, for 14 days) resulted in robust antidepressant-like effects (increased sucrose consumption and decreased immobility time). The antidepressant-like effects of JSH-23 were mostly accompanied by a reduction in levels of pro-inflammatory mediators in the brain. On the other hand, JSH-23 did not reduce amphetamine-induced hyperactivity. Conclusions: Altogether, these data suggest that NF-κB may be a potential therapeutic target for pharmacological interventions for depression.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje