Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL.
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.
Aonurm-Helm
Anu
A
Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Tartu, Estonia.
Jurgenson
Monika
M
Zharkovsky
Tamara
T
Sonn
Katrin
K
Berezin
Vladimir
V
Bock
Elisabeth
E
Zharkovsky
Alexander
A
D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D005346:Fibroblast Growth Factors / Q000819:agonists / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000819:agonists* / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors