Depression‐like behaviour in neural cell adhesion molecule (NCAM)‐deficient mice and its reversal by an NCAM‐derived peptide, FGL

Abstract

The neural cell adhesion molecule (NCAM) plays a pivotal role in brain plasticity. Brain plasticity itself has a crucial role in the development of depression. The aim of this study was to analyze whether NCAM-deficient (NCAM(-/-)) mice exhibit depression-like behaviour and whether a peptide termed FGL, derived from the NCAM binding site for the fibroblast growth factor (FGF) receptor, is able to reverse the depression-like signs in NCAM(-/-) mice. Our study showed that NCAM(-/-) mice demonstrated increased freezing time in the tail-suspension test and reduced preference for sucrose consumption in the sucrose preference test, reduced adult neurogenesis in the dentate gyrus and reduced levels of the phosphorylated cAMP response element-binding protein (pCREB) in the hippocampus. FGL administered acutely or repeatedly reduced depression-like behaviour in NCAM(-/-) mice without having an effect on their wild-type littermates. Repeated administration of FGL enhanced survival of the newly born neurons in NCAM(-/-) mice and increased the levels of pCREB in both NCAM(+/+) and NCAM(-/-) mice. In conclusion, our data demonstrate that NCAM deficiency in mice results in a depression-like phenotype which can be reversed by the acute or repeated administration of FGL. The results also suggest a role of the deficit in NCAM signalling through the FGF receptor in depression.

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

“…73,74 Similarly, animal models further support the role of the FGF system in depression and its potential involvement in antidepressant treatment. 75,76 Intraventricular administration of FGF-2 was also shown to have an antidepressive-like effect in rats. 77 However, although the theory identifying hippocampal neurogenesis as a cause of depression has long been propagated, 78 doubts have recently been raised concerning its soundness.…”

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression

“…This is pertinent for addiction, as it is posited to involve the subversion of reward-related learning and there is also evidence that addiction phenotypes alter expression levels of polysialylated NCAM in the brain [52][53][54]. Similarly, depressive episodes have been linked to neuronal atrophy, whilst efficacious antidepressant treatment increases neurogenesis and enhances neural plasticity [55,56] and there is evidence that NCAM levels may be associated with MDD (and related behaviors) [57][58][59].…”

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

“…Neural cell adhesion molecule (NCAM), a prominent member of the immunoglobulin superfamily of adhesion molecules, is one of the best-characterized cell adhesion molecules (CAMs) with regard to its involvement in brain plasticity, remodeling and formation of synapses, and its ability to modulate synaptic characteristics (Aonurm-Helm et al, 2008;Cunningham et al, 1987). The expression levels of NCAM and its binding properties are crucial for neural remodeling and synaptic function.…”