title: Sertraline reduces IL-1β and TNF-α mRNA expression and overcomes their rise induced by seizures in the rat hippocampus.
abstract: We recently discovered that the antidepressant sertraline is an effective inhibitor of hippocampus presynaptic Na+ channel permeability in vitro and of tonic-clonic seizures in animals in vivo. Several studies indicate that the pro-inflammatory cytokines in the central nervous system are increased in epilepsy and depression. On the other hand inhibition of Na+ channels has been shown to decrease pro-inflammatory cytokines in microglia. Therefore, the possibility that sertraline could overcome the rise in pro-inflammatory cytokine expression induced by seizures has been investigated. For this purpose, IL-1β and TNF-α mRNA expression was determined by RT-PCR in the hippocampus of rats administered once, or for seven consecutive days with sertraline at a low dose (0.75 mg/kg). The effect of sertraline at doses within the range of 0.75 to 25 mg/kg on the increase in IL-1β and TNF-α mRNA expression accompanying generalized tonic-clonic seizures, and increase in the pro-inflammatory cytokines expression induced by lipopolysaccharide was also investigated. We found that under basal conditions, a single 0.75 mg/kg sertraline dose decreased IL-1β mRNA expression, and also TNF-α expression after repeated doses. The increase in IL-1β and TNF-α expression induced by the convulsive agents and by the inoculation of lipopolysaccharide in the hippocampus was markedly reduced by sertraline also. Present results indicate that a reduction of brain inflammatory processes may contribute to the anti-seizure sertraline action, and that sertraline can be safely and successfully used at low doses to treat depression in epileptic patients.
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
authors.forename: María
authors.initials: M
authors.lastname: Sitges
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Gómez
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Distrito Federal, México.
authors.forename: Blanca I
authors.initials: BI
authors.lastname: Aldana
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000009:adverse effects; D012333:RNA, Messenger; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020280:Sertraline / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020280:Sertraline; D010433:Pentylenetetrazole