PMID- 26499173
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20161230
IS  - 1873-7862 (Electronic)
IS  - 0924-977X (Linking)
VI  - 25
IP  - 12
DP  - 2015 Dec
TI  - NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems 
      in brain - Restoration by chronic amitriptyline.
PG  - 2394-403
LID - S0924-977X(15)00326-0 [pii]
LID - 10.1016/j.euroneuro.2015.10.001 [doi]
AB  - 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.
CI  - Copyright (c) 2015 Elsevier B.V. and ECNP. All rights reserved.
FAU - Aonurm-Helm, Anu
AU  - Aonurm-Helm A
AD  - Institute of Biomedicine and Translational Medicine, Department of Pharmacology, 
      University of Tartu, 50411 Tartu, Estonia. Electronic address: anu.aonurm@ut.ee.
FAU - Anier, Kaili
AU  - Anier K
AD  - Institute of Biomedicine and Translational Medicine, Department of Pharmacology, 
      University of Tartu, 50411 Tartu, Estonia.
FAU - Zharkovsky, Tamara
AU  - Zharkovsky T
AD  - Institute of Biomedicine and Translational Medicine, Department of Pharmacology, 
      University of Tartu, 50411 Tartu, Estonia.
FAU - Castren, Eero
AU  - Castren E
AD  - Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, Finland.
FAU - Rantamaki, Tomi
AU  - Rantamaki T
AD  - Neuroscience Center, University of Helsinki, P.O. Box 56, Helsinki, Finland.
FAU - Stepanov, Vladimir
AU  - Stepanov V
AD  - Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia.
FAU - Jarv, Jaak
AU  - Jarv J
AD  - Institute of Chemistry, University of Tartu, 50411 Tartu, Estonia.
FAU - Zharkovsky, Alexander
AU  - Zharkovsky A
AD  - Institute of Biomedicine and Translational Medicine, Department of Pharmacology, 
      University of Tartu, 50411 Tartu, Estonia.
LA  - eng
PT  - Journal Article
DEP - 20151021
PL  - Netherlands
TA  - Eur Neuropsychopharmacol
JT  - European neuropsychopharmacology : the journal of the European College of 
      Neuropsychopharmacology
JID - 9111390
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neural Cell Adhesion Molecules)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, mouse)
RN  - 1806D8D52K (Amitriptyline)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/*therapeutic use
MH  - Amitriptyline/*therapeutic use
MH  - Animals
MH  - Brain/metabolism
MH  - *Brain Diseases, Metabolic/drug therapy/genetics/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Disease Models, Animal
MH  - Electrochemical Techniques
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neural Cell Adhesion Molecules/*deficiency/genetics
MH  - Phosphorylation/drug effects/genetics
MH  - Protein Binding/drug effects/genetics
MH  - Receptor, trkB/metabolism
MH  - Serotonin/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
OTO - NOTNLM
OT  - Antidepressant
OT  - Neurotrophins
OT  - Plasticity
OT  - Serotonergic neurotransmission
EDAT- 2015/10/27 06:00
MHDA- 2016/10/07 06:00
CRDT- 2015/10/27 06:00
PHST- 2015/05/21 00:00 [received]
PHST- 2015/08/13 00:00 [revised]
PHST- 2015/10/05 00:00 [accepted]
PHST- 2015/10/27 06:00 [entrez]
PHST- 2015/10/27 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
AID - S0924-977X(15)00326-0 [pii]
AID - 10.1016/j.euroneuro.2015.10.001 [doi]
PST - ppublish
SO  - Eur Neuropsychopharmacol. 2015 Dec;25(12):2394-403. doi: 
      10.1016/j.euroneuro.2015.10.001. Epub 2015 Oct 21.