کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10299046 | 539680 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
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چکیده انگلیسی
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 NCAMâ/â mice. This SERT reduction was already evident during early postnatal development. [3H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAMâ/â mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAMâ/â mice. NCAMâ/â 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 NCAMâ/â mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Neuropsychopharmacology - Volume 25, Issue 12, December 2015, Pages 2394-2403
Journal: European Neuropsychopharmacology - Volume 25, Issue 12, December 2015, Pages 2394-2403
نویسندگان
Anu Aonurm-Helm, Kaili Anier, Tamara Zharkovsky, Eero Castrén, Tomi Rantamäki, Vladimir Stepanov, Jaak Järv, Alexander Zharkovsky,