Fluoxetine attenuates kainic acid-induced neuronal cell death in the mouse hippocampus

Yinchuan Jin, Chae Moon Lim, Seung Woo Kim, Ju Young Park, Ji Seon Seo, Pyung Lim Han, Sung Hwa Yoon, Ja Kyeong Lee

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and one of the commonly prescribed antidepressants. Numerous clinical observations and animal studies indicate that fluoxetine enhances the anticonvulsant potencies of several antiepileptic drugs. In the previous report, we showed that fluoxetine strongly protects against delayed cerebral ischemic injury. In the present study, the authors investigated whether fluoxetine has a beneficial effect on KA-induced neuronal cell death. An intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 μg) of KA produced typical neuronal cell death both in CA1 and CA3 regions of the hippocampus. Although, there was no significant difference in the time course or severity of epileptic behavior, the systemic administration of fluoxetine 30 min before KA administration significantly attenuated this neuronal cell death. Fluoxetine was found to suppress neuronal cell loss when injected at 10 mg/kg and the effect was enhanced at 50 mg/kg. Furthermore, this fluoxetine-induced neuroprotection was accompanied by marked improvements in memory impairment, as determined by passive avoidance tests. KA-induced gliosis and proinflammatory marker (COX-2, IL-1β, and TNF-α) inductions were also suppressed by fluoxetine administration. It is interesting to note here that fluoxetine treatment suppressed NF-κB activity dose-dependently in KA-treated mouse brains, suggesting that this explains in part its anti-inflammatory effect. Together, these results suggest that fluoxetine has therapeutic potential in terms of suppressing KA-induced pathogenesis in the brain, and that these neuroprotective effects are associated with its anti-inflammatory effects.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
JournalBrain Research
Volume1281
DOIs
StatePublished - 24 Jul 2009

Keywords

  • Fluoxetine
  • Inflammation
  • KA
  • NF-κB
  • Neuroprotection

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