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

TY - JOUR

T1 - Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL

AU - Aonurm-Helm, Anu

AU - Jurgenson, Monika

AU - Zharkovsky, Tamara

AU - Sonn, Katrin

AU - Berezin, Vladimir

AU - Bock, Elisabeth

AU - Zharkovsky, Alexander

N1 - Keywords: Animals; Atrophy; Brain; Cell Survival; Cyclic AMP Response Element-Binding Protein; Depressive Disorder; Disease Models, Animal; Fibroblast Growth Factors; Hippocampus; Mice; Mice, Knockout; Neural Cell Adhesion Molecules; Neurogenesis; Neurons; Receptors, Fibroblast Growth Factor; Treatment Outcome; Up-Regulation

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1111/j.1460-9568.2008.06471.x

DO - 10.1111/j.1460-9568.2008.06471.x

M3 - Journal article

C2 - 18973581

SN - 0953-816X

VL - 28

SP - 1618

EP - 1628

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

IS - 8

ER -