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

• Published in: The European journal of neuroscience Vol. 28; no. 8; pp. 1618 - 1628
• Main Authors: Aonurm-Helm, Anu, Jurgenson, Monika, Zharkovsky, Tamara, Sonn, Katrin, Berezin, Vladimir, Bock, Elisabeth, Zharkovsky, Alexander
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2008
• Subjects: Animals; Atrophy - drug therapy; Atrophy - physiopathology; Atrophy - prevention & control; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cell Survival - drug effects; Cell Survival - genetics; Cyclic AMP Response Element-Binding Protein - drug effects; Cyclic AMP Response Element-Binding Protein - metabolism; depression-like phenotype; Depressive Disorder - drug therapy; Depressive Disorder - genetics; Depressive Disorder - physiopathology; Disease Models, Animal; FGL peptide; Fibroblast Growth Factors - agonists; Fibroblast Growth Factors - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Mice; Mice, Knockout; NCAM knockout; Neural Cell Adhesion Molecules - agonists; Neural Cell Adhesion Molecules - genetics; Neural Cell Adhesion Molecules - pharmacology; Neural Cell Adhesion Molecules - therapeutic use; neurogenesis; Neurogenesis - drug effects; Neurogenesis - genetics; Neurons - drug effects; Neurons - metabolism; pCREB; Receptors, Fibroblast Growth Factor - agonists; Receptors, Fibroblast Growth Factor - metabolism; Treatment Outcome; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2008.06471.x

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.