Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations
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Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.
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Residual changes and reported impairments in DG synaptic plasticity may account for the re-appearance of depressive, anxiety and cognitive deficits on uCMS re-exposure.
“These residual changes, together with reported impairments in DG synaptic plasticity9, 28, 29 may account for the re-appearance of depressive, anxiety and cognitive deficits on uCMS re-exposure.”
From Adult hippocampal neuroplasticity triggers susceptibility to recurrent depression (2017) · cites this paper as [28]
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SEROTONIN IN EMOTIONAL MEMORY PROCESSES: NEUROPHARMACOLOGICAL STUDIES WITH EMPHASIS ON DEPRESSION
Eriksson, T. (2012) · Figshare
- Authors
- Bisaz, R., & Sandi, C.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Sandi, Carmen
- ORCID
- Sandi, Carmen
- Venue
- Stress
- Publisher
- Informa UK Limited
- Published
- 2011-09-22
- Volume
- 15
- Issue
- 2
- Pages
- 195-206
- ISSN
- 1025-3890 (ISSN-L)
- 1607-8888
- OpenAlex
- W1821168534
- Cited by
- 28
- References
- 89
- Citations by year
- 2023: 2 · 2020: 2 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 3 · 2013: 6 · 2012: 7
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stress (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (122691, 120791, 108102, 122697, 310000, 3100A0)
- FP7 Health
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- CD56, chronic stress, depression-like behavior, spatial learning and memory, conditional knockout mice, forebrain, vulnerability to stress, hippocampus, prefrontal cortex, tail suspension test, water maze
- MeSH terms
- Animals, Behavior, Animal, Hippocampus, Male, Memory, Mice, Inbred C57BL, Neurons, Stress, Psychological, Prosencephalon, Prefrontal Cortex, Mice, Knockout, Maze Learning, Neural Cell Adhesion Molecules, Mice
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