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NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline.
- Source :
-
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology [Eur Neuropsychopharmacol] 2015 Dec; Vol. 25 (12), pp. 2394-403. Date of Electronic Publication: 2015 Oct 21. - Publication Year :
- 2015
-
Abstract
- Mood disorders are associated with alterations in serotonergic system, deficient BDNF (brain-derived neurotrophic factor) signaling and abnormal synaptic plasticity. Increased degradation and reduced functions of NCAM (neural cell adhesion molecule) have recently been associated with depression and NCAM deficient mice show depression-related behavior and impaired learning. The aim of the present study was to investigate potential changes in serotonergic and BDNF systems in NCAM knock-out mice. Serotonergic nerve fiber density and SERT (serotonin transporter) protein levels were robustly reduced in the hippocampus, prefrontal cortex and basolateral amygdala of adult NCAM(-)(/-) mice. This SERT reduction was already evident during early postnatal development. [(3)H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAM(-)(/-) mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAM(-)(/-) mice. NCAM(-)(/-) mice also showed a dramatic reduction in the BDNF protein levels in the hippocampus and prefrontal cortex. This BDNF deficiency was associated with reduced phosphorylation of its receptor TrkB. Importantly, chronic administration of antidepressant amitriptyline partially or completely restored these changes in serotonergic and BDNF systems, respectively. In conclusion, NCAM deficiency lead to prominent and persistent abnormalities in brain serotonergic and BDNF systems, which likely contributes to the behavioral and neurobiological phenotype of NCAM(-/-) mice.<br /> (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)
- Subjects :
- Animals
Brain metabolism
Disease Models, Animal
Electrochemical Techniques
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation drug effects
Gene Expression Regulation genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neural Cell Adhesion Molecules genetics
Phosphorylation drug effects
Phosphorylation genetics
Protein Binding drug effects
Protein Binding genetics
Receptor, trkB metabolism
Serotonin Plasma Membrane Transport Proteins metabolism
Adrenergic Uptake Inhibitors therapeutic use
Amitriptyline therapeutic use
Brain Diseases, Metabolic drug therapy
Brain Diseases, Metabolic genetics
Brain Diseases, Metabolic metabolism
Brain-Derived Neurotrophic Factor metabolism
Neural Cell Adhesion Molecules deficiency
Serotonin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7862
- Volume :
- 25
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26499173
- Full Text :
- https://doi.org/10.1016/j.euroneuro.2015.10.001