Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Yan Li, Aicha Abdourahman, Joseph A. Tamm, Alan Pehrson, Connie Sánchez, Maria Gulinello

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression. Twelve-month-old female C57BL/6 mice exhibited impaired visuospatial memory in the novel object placement (location) task associated with reduced expression of several plasticity-related genes. Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in middle-aged mice. Vortioxetine, but not fluoxetine, increased hippocampal expression of several neuroplasticity-related genes in middle-aged mice (e.g., Nfkb1, Fos, Fmr1, Camk2a, Arc, Shank1, Nlgn2, and Rab3a). Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. Thus, a change in the expression of multiple genes involved in neuronal plasticity by antidepressant treatment was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.

Original languageEnglish
Pages (from-to)70-82
Number of pages13
JournalPharmacology Biochemistry and Behavior
Volume135
DOIs
StatePublished - 3 Jun 2015

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Gene expression
Antidepressive Agents
Neuronal Plasticity
Plasticity
Fluoxetine
Cell proliferation
Genes
Stem cells
Gene Expression
Intercellular Signaling Peptides and Proteins
Stem Cells
Cell Proliferation
Depression
Data storage equipment
Serotonin Uptake Inhibitors
Inbred C57BL Mouse
Cognition
Brain Stem
Rodentia
Brain

Keywords

  • Antidepressant
  • Forced swim test
  • Novel object placement
  • SSRI (selective serotonin reuptake inhibitor)
  • Spatial memory
  • Vortioxetine

Cite this

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title = "Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice",
abstract = "Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression. Twelve-month-old female C57BL/6 mice exhibited impaired visuospatial memory in the novel object placement (location) task associated with reduced expression of several plasticity-related genes. Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in middle-aged mice. Vortioxetine, but not fluoxetine, increased hippocampal expression of several neuroplasticity-related genes in middle-aged mice (e.g., Nfkb1, Fos, Fmr1, Camk2a, Arc, Shank1, Nlgn2, and Rab3a). Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. Thus, a change in the expression of multiple genes involved in neuronal plasticity by antidepressant treatment was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.",
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Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice. / Li, Yan; Abdourahman, Aicha; Tamm, Joseph A.; Pehrson, Alan; Sánchez, Connie; Gulinello, Maria.

In: Pharmacology Biochemistry and Behavior, Vol. 135, 03.06.2015, p. 70-82.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Li, Yan

AU - Abdourahman, Aicha

AU - Tamm, Joseph A.

AU - Pehrson, Alan

AU - Sánchez, Connie

AU - Gulinello, Maria

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