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Cited by 79Neurogenesis and neuroplasticity mechanismsTreatment of Major DepressionNeuroscience and Neuropharmacology Research

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

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Li, Yan, Abdourahman, Aicha, Tamm, Joseph A., Pehrson, Alan L., Sánchez, Connie, Gulinello, Maria·2015·Pharmacology Biochemistry and Behavior
DOI 10.1016/j.pbb.2015.05.013
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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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  • Research on memory in rodents and monkeys suggests that both spatial (what-where) and temporal (what-when) elements of memory decline alongside typical age-related changes within the brain.

    “research on memory in rodents and monkeys, although again not strictly in line with episodic-like memory criteria, suggests that both spatial (what–where) [139–142] and temporal (what–when) [142,143] elements of memory decline alongside typical age-related changes within the brain.”

    From Is episodic-like memory <i>like</i> episodic memory? (2024) · cites this paper as [141]

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Authors
Li, Y., Abdourahman, A., Tamm, J. A., Pehrson, A. L., Sánchez, C., & Gulinello, M.
Affiliations
  • Lundbeck (United States) (US)
  • Albert Einstein College of Medicine (US)
Corresponding author
Gulinello, Maria
ORCID
Venue
Pharmacology Biochemistry and Behavior
Publisher
Elsevier BV
Published
2015-08
Volume
135
Pages
70-82
ISSN
0091-3057 (ISSN-L)
DOI
10.1016/j.pbb.2015.05.013
OpenAlex
W613978054
Semantic Scholar
53cab908728efdb34cf73ab7600418e85fc4ccfa
Cited by
79
References
147
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 14 · 2016: 7 · 2015: 3
FWCI
4.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmacology Biochemistry and Behavior (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • H. Lundbeck A/S
  • Takeda Pharmaceuticals, Inc.
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
age-related cognitive decline, antidepressants, vortioxetine, fluoxetine, synaptic plasticity, hippocampus, stem cell proliferation, visuospatial memory, depression-like behavior, middle-aged mice, growth factors, selective serotonin reuptake inhibitors
MeSH terms
Vortioxetine, Aging, Animals, Antidepressive Agents, Cognition Disorders, Female, Fluoxetine, Hippocampus, Mice, Inbred C57BL, Motor Activity, Neuronal Plasticity, Piperazines, Sulfides, Swimming, Gene Expression, Recognition, Psychology, Intercellular Signaling Peptides and Proteins, Cell Proliferation, Serotonin Plasma Membrane Transport Proteins, Mice, Neural Stem Cells

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