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 -