title: Early-life fluoxetine exposure reduced functional deficits after hypoxic-ischemia brain injury in rat pups.
abstract: 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.
authors.affiliation: Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Guang University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Chang
authors.forename: Shun-Fen
authors.initials: SF
authors.lastname: Tzeng
authors.forename: Lung
authors.initials: L
authors.lastname: Yu
authors.forename: A-Min
authors.initials: AM
authors.lastname: Huang
authors.forename: Hsueh-Te
authors.initials: HT
authors.lastname: Lee
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Chien-Jung
authors.initials: CJ
authors.lastname: Ho
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000633:toxicity; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D001973:Bromodeoxyuridine / Q000633:toxicity; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology / Q000523:psychology*; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents; D009929:Organ Size / Q000502:physiology; D010766:Phosphorylation; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D016704:Synapsins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000963:Antimetabolites; D019208:Brain-Derived Neurotrophic Factor; D001973:Bromodeoxyuridine; D017362:Cyclic AMP Response Element-Binding Protein; D005473:Fluoxetine; D018696:Neuroprotective Agents; D017367:Selective Serotonin Reuptake Inhibitors; D016704:Synapsins