TY - JOUR

T1 - Sertraline reduces IL-1β and TNF-α mRNA expression and overcomes their rise induced by seizures in the rat hippocampus

AU - Sitges, María

AU - Gómez, Carlos D.

AU - Aldana, Blanca I.

N1 - Publisher Copyright: © 2014 Sitges et al.

PY - 2014/11/3

Y1 - 2014/11/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84909606645&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0111665

DO - 10.1371/journal.pone.0111665

M3 - Journal article

C2 - 25364907

AN - SCOPUS:84909606645

VL - 9

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e111665

ER -