期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 529, 期 12, 页码 3194-3205出版社
WILEY
DOI: 10.1002/cne.25155
关键词
depression; electron microscopy; hippocampus; RRID; AB_11212156; RRID; AB_1658870; RRID; AB_2039881; RRID; AB_2040224; RRID; AB_2092366; RRID; AB_2113447; RRID; AB_2313773; RRID; AB_258091; RRID; AB_258103; RRID; AB_444181; RRID; AB_634092; RRID; AB_887694; RRID; AB_954427; synapse; synaptic plasticity
资金
- European Union Project (GRIPANNT) [LSCHM-CT2005-005320]
- European Union Project (KARTRAP) [QLG3-CT2001-02089]
- University of Oslo
This study identified significant concentration differences in synaptic proteins such as NMDAR, Arc and syntaxin-1 in a congenital rat learned helplessness model of depression. 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.
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.
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