Early-life fluoxetine exposure reduced functional deficits after hypoxic-ischemia brain injury in rat pups

Ying Chao Chang, Shun Fen Tzeng, Lung Yu, A. Min Huang, Hsueh Te Lee, Chao Ching Huang, Chien Jung Ho

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


Neuroplasticity after perinatal programming may allow for neuroprotection against hypoxic-ischemia (HI) at birth. The cAMP response element-binding protein (CREB) is a key mediator of stimulus-induced nuclear responses that underlie survival, memory and plasticity of nervous system. Chronic treatment of fluoxetine, a selective serotonin reuptake inhibitor, can upregulate CREB activation in the hippocampus. We examined whether fluoxetine administration before HI may protect against neonatal HI brain injury through CREB-mediated mechanisms. We found that low-dose fluoxetine pretreatment in a neonatal HI brain injury model significantly reduced functional deficits at adulthood. The neuroprotective mechanisms were associated with increased CREB phosphorylation and increased brain-derived neurotrophic factor and synapsin I mRNA expression in the hippocampus. Neurogenesis also increased because of greater precursor cell survival in the hippocampal dentate gyrus. These findings suggest that functional deficits after HI in the developing brain can be reduced by agents that enhance neural plasticity and neurogenesis through CREB activation.

Original languageEnglish
Pages (from-to)101-113
Number of pages13
JournalNeurobiology of Disease
Issue number1
Publication statusPublished - Oct 2006
Externally publishedYes


  • Brain-derived neurotrophic factor
  • Fluoxetine
  • Hypoxic-ischemia
  • Neurogenesis
  • Newborn
  • cAMP response element-binding protein

ASJC Scopus subject areas

  • Neurology


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