Causal evidence for the involvement of the neural cell adhesion molecule, NCAM, in chronic stress‐induced cognitive impairments

Bisaz, Reto; Schachner, Melitta; Sandi, Carmen

doi:10.1002/hipo.20723

Cited by 51 publications

(72 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With respect to emotional and anxiety-related behavior, constitutive NCAMKOs were characterized with higher levels of anxiety in several tests, including the EPM, light-dark box and OF test (Aonurm-Helm et al, 2008). However, previous studies have shown that NCAM-cKO is associated with decreased anxiety in the elevated zero maze in animals under basal conditions (Bisaz et al, 2009), whereas we did not find differences concerning the time spent in the center of the open field under baseline conditions, but following stress. Further studies are necessary to clarify the differential impact of conditional and constitutive NCAM deletion together with stress exposure on anxiety-like behavior in mice.…”

Section: Discussioncontrasting

confidence: 85%

The interplay of conditional NCAM-knockout and chronic unpredictable stress leads to increased aggression in mice

Kohl

Riccio

Grosse

et al. 2013

Stress

Self Cite

View full text Add to dashboard Cite

The neural cell adhesion molecule (NCAM) is a key regulator of brain plasticity. Substantial evidence indicates that NCAM is down-regulated by exposure to sustained stress and chronic stress seems to lead to increased aggression. In addition, constitutional NCAM deletion in mice has been shown to lead to increased intermale aggression and altered emotionality Forebrain-specific postnatal NCAM knockout was previously shown to impair cognitive function, particularly when animals were exposed to subchronic stress, but the effects on emotional and social behavior remain unclear. In this study, we investigated the potential interplay of a forebrain-specific postnatal NCAM deletion and exposure to different lengths of repeated stress (i.e. subchronic: 14 days; chronic: 29 days) on aggressive and emotional behavior. Our results show that postnatal deletion of NCAM in the forebrain leads to increased aggression and altered emotionality depending on the duration of stress, whereas conditional NCAM knockout has no basal impact on these behaviors. These findings support the involvement of NCAM in the regulation of emotional and aggressive behaviors, suggesting that diminished NCAM expression might be a critical vulnerability factor for the development of these behavioral alterations under repeated exposure to stress.

show abstract

Section: Discussioncontrasting

confidence: 85%

The interplay of conditional NCAM-knockout and chronic unpredictable stress leads to increased aggression in mice

Kohl

Riccio

Grosse

et al. 2013

Stress

Self Cite

View full text Add to dashboard Cite

show abstract

“…UCMS protocol was described before (Bisaz et al, 2011;Bisaz and Sandi, 2012) and used with some modifications. Non-stressed and stressed groups were housed in separated and closed housing racks located in the same room during the duration of the stress procedure.…”

Section: Unpredictable Chronic Mild Stress (Ucms) and Chronic Fluoxetmentioning

confidence: 99%

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Jedynak

Kos

Sandi

et al. 2014

Journal of Psychiatric Research

Self Cite

View full text Add to dashboard Cite

a b s t r a c tThe neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

show abstract

“…Additionally, while repeated measures ANOVAs indicated a significant effect in the "trial" factor for both ages (adults: F (3,60) ¼ 7.351, P ¼ 0.0003; aged: F (3,60) ¼ 8.632, P , 0.0001), a lack of significance in the "trial × genotype" interaction in both age groups (adults: F (3,60) ¼ 0.274, P ¼ 0.84; aged: F (3,60) ¼ 0.648, P ¼ 0.59) was also observed. Substantial data in the literature indicate that NCAM deficiency manifests as sporadic impairments in individual trials (Bukalo et al 2004;Bisaz et al 2011;Bisaz and Sandi 2012); therefore, we also applied unpaired Student's t-tests to individual trial blocks. Indeed, significant differences between genotypes were observed in the first trial block in adult mice ( Fig.…”

Section: Delayed Matching-to-place (Dmp) Task In the Morris Water Mazementioning

confidence: 99%

“…In rodents, behavioral manipulations associated with structural and functional alterations in the hippocampus, such as chronic stress, are reportedly accompanied by a reduction of NCAM expression levels, predominately in the hippocampus, but also in other forebrain areas (Sandi et al 2001;Venero et al 2002;Alfonso et al 2006;Sandi and Touyarot 2006;Huang et al 2008;Bisaz et al 2011). Thus, NCAM reduction has been proposed to contribute to cognitive disturbances induced by stress (Sandi 2004;Sandi and Bisaz 2007).…”

mentioning

confidence: 99%

Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule

et al. 2013

Self Cite

View full text Add to dashboard Cite

Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However, whether aging is associated with NCAM alterations that might contribute to age-related cognitive decline is not currently known. In this study, we determined whether conditional NCAM-deficient mice display increased vulnerability to age-related cognitive and emotional alterations. We assessed the NCAM expression levels in the hippocampus and medial prefrontal cortex (mPFC) and characterized the performance of adult and aged conditional NCAM-deficient mice and their age-matched wild-type littermates in a delayed matching-to-place test in the Morris water maze and a delayed reinforced alternation test in the T-maze. Although aging in wild-type mice is associated with an isoform-specific reduction of NCAM expression levels in the hippocampus and mPFC, these mice exhibited only mild impairments in working/episodic-like memory performance. However, aged conditional NCAM-deficient mice displayed pronounced impairments in both the delayed matching-to-place and the delayed reinforced alternation tests. Importantly, the deficits of aged NCAM-deficient mice in these working/episodic-like memory tasks could not be attributed to increased anxiety-like behaviors or to differences in locomotor activity. Taken together, these data indicate that reduced NCAM expression in the forebrain might be a critical factor for the occurrence of cognitive impairments during aging.[Supplemental material is available for this article.]One of the hallmarks of normal aging is a gradual decline in cognitive function associated with the progressive reduction of structural and functional plasticity in brain regions that play a key role in cognitive functions, such as the hippocampus and the prefrontal cortex (Seki and

show abstract

Causal evidence for the involvement of the neural cell adhesion molecule, NCAM, in chronic stress‐induced cognitive impairments

Cited by 51 publications

References 100 publications

The interplay of conditional NCAM-knockout and chronic unpredictable stress leads to increased aggression in mice

The interplay of conditional NCAM-knockout and chronic unpredictable stress leads to increased aggression in mice

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule

Contact Info

Product

Resources

About