Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but does not improve functional recovery after traumatic brain injury.
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Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but does not improve functional recovery after traumatic brain injury. / Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M; Kim, Sharon; Noble-Haeusslein, Linda J; Liu, Jialing.
in: J NEUROTRAUM, Jahrgang 28, Nr. 2, 2, 2011, S. 259-268.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Fluoxetine increases hippocampal neurogenesis and induces epigenetic factors but does not improve functional recovery after traumatic brain injury.
AU - Wang, Yonggang
AU - Neumann, Melanie
AU - Hansen, Katharina
AU - Hong, Shuwhey M
AU - Kim, Sharon
AU - Noble-Haeusslein, Linda J
AU - Liu, Jialing
PY - 2011
Y1 - 2011
N2 - The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10?mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits.
AB - The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10?mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits.
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Recovery of Function/drug effects/physiology
KW - Brain Injuries/drug therapy/pathology/physiopathology
KW - Epigenesis, Genetic/drug effects/physiology
KW - Fluoxetine/pharmacology/therapeutic use
KW - Hippocampus/cytology/drug effects/physiology
KW - Neurogenesis/drug effects/physiology
KW - Animals
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Recovery of Function/drug effects/physiology
KW - Brain Injuries/drug therapy/pathology/physiopathology
KW - Epigenesis, Genetic/drug effects/physiology
KW - Fluoxetine/pharmacology/therapeutic use
KW - Hippocampus/cytology/drug effects/physiology
KW - Neurogenesis/drug effects/physiology
M3 - SCORING: Journal article
VL - 28
SP - 259
EP - 268
JO - J NEUROTRAUM
JF - J NEUROTRAUM
SN - 0897-7151
IS - 2
M1 - 2
ER -
