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 L. Pehrson, Connie Sánchez, Maria E. Gulinello

Research output: Contribution to journalArticle

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

Fingerprint

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
  • Spatial memory
  • SSRI (selective serotonin reuptake inhibitor)
  • Vortioxetine

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

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 L.; Sánchez, Connie; Gulinello, Maria E.

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

Research output: Contribution to journalArticle

@article{e8427c5e4a3042c9b9fddaef13fddd0f,
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.",
keywords = "Antidepressant, Forced swim test, Novel object placement, Spatial memory, SSRI (selective serotonin reuptake inhibitor), Vortioxetine",
author = "Yan Li and Aicha Abdourahman and Tamm, {Joseph A.} and Pehrson, {Alan L.} and Connie S{\'a}nchez and Gulinello, {Maria E.}",
year = "2015",
month = "6",
day = "3",
doi = "10.1016/j.pbb.2015.05.013",
language = "English (US)",
volume = "135",
pages = "70--82",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

AU - Li, Yan

AU - Abdourahman, Aicha

AU - Tamm, Joseph A.

AU - Pehrson, Alan L.

AU - Sánchez, Connie

AU - Gulinello, Maria E.

PY - 2015/6/3

Y1 - 2015/6/3

N2 - 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.

AB - 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.

KW - Antidepressant

KW - Forced swim test

KW - Novel object placement

KW - Spatial memory

KW - SSRI (selective serotonin reuptake inhibitor)

KW - Vortioxetine

UR - http://www.scopus.com/inward/record.url?scp=84930680422&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930680422&partnerID=8YFLogxK

U2 - 10.1016/j.pbb.2015.05.013

DO - 10.1016/j.pbb.2015.05.013

M3 - Article

VL - 135

SP - 70

EP - 82

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

ER -