Changes in concentrations of NMDA receptor subunit GluN2B, Arc and syntaxin-1 in dorsal hippocampus Schaffer collateral synapses in a rat learned helplessness model of depression

Bieler, M, Hussain, S, Daaland, ESB, Mirrione, M. M., Henn, F. A., Davanger, S (April 2021) Changes in concentrations of NMDA receptor subunit GluN2B, Arc and syntaxin-1 in dorsal hippocampus Schaffer collateral synapses in a rat learned helplessness model of depression. The Journal of Comparative Neurology, 529 (12). pp. 3194-3205.

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Abstract

Major depressive disorder involves changes in synaptic structure and function, but the molecular underpinnings of these changes are still not established. In an initial pilot experiment, whole-brain synaptosome screening with quantitative western blotting was performed to identify synaptic proteins that may show concentration changes in a congenital rat learned helplessness model of depression. We found that the N-methyl-d-aspartate receptor (NMDAR) subunits GluN2A/GluN2B, activity-regulated cytoskeleton-associated protein (Arc) and syntaxin-1 showed significant concentration differences between congenitally learned helpless (LH) and nonlearned helpless (NLH) rats. Having identified these three proteins, we then performed more elaborate quantitative immunogold electron microscopic analyses of the proteins in a specific synapse type in the dorsal hippocampus: the Schaffer collateral synapse in the CA1 region. We expanded the setup to include also unstressed wild-type (WT) rats. The concentrations of the proteins in the LH and NLH groups were compared to WT animals. In this specific synapse, we found that the concentration of NMDARs was increased in postsynaptic spines in both LH and NLH rats. The concentration of Arc was significantly increased in postsynaptic densities in LH animals as well as in presynaptic cytoplasm of NLH rats. The concentration of syntaxin-1 was significantly increased in both presynaptic terminals and postsynaptic spines in LH animals, while pre- and postsynaptic syntaxin-1 concentrations were significantly decreased in NLH animals. These protein changes suggest pathways by which synaptic plasticity may be increased in dorsal hippocampal Schaffer collateral synapses during depression, corresponding to decreased synaptic stability

Item Type: Paper
Subjects: bioinformatics
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > mental disorders
diseases & disorders > mental disorders > mood disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > NMDA receptor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > animal
organism description > animal behavior
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cytoskeletal proteins
diseases & disorders > mental disorders > mood disorders > depression
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organism description > animal > mammal
organs, tissues, organelles, cell types and functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Depositing User: Sasha Luks-Morgan
Date: 12 April 2021
Date Deposited: 16 Jun 2021 14:42
Last Modified: 17 Jan 2024 20:18
Related URLs:
URI: https://repository.cshl.edu/id/eprint/40210

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