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P2‐123: The Candidate Therapeutic Target in a Rat Model of Depression
Author(s) -
Shi Yan
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1493
Subject(s) - hippocampus , chronic stress , behavioural despair test , dendritic spine , hippocampal formation , psychology , medicine , proteome , endocrinology , open field , antidepressant , chemistry , neuroscience , biochemistry
Background:After chronic stress, rats’ spontaneous activity weakened in the open-field experiments, the immobility time was significantly longer in forced swimming test, and the percentage of sucrose consumption reduced. Chronic stress-induced depressive rats showed spatial learning and memory deficit with decreasing of neurons and dendritic spines in hippocampus. Methods: After seven days of water maze learning and training, spatial learning improved depressive symptoms. However, the rats without learning showed no significant change. The study was performed on hippocampus of the learning and non-learning depression rats. Using TMT labeling and HPLC fractionation followed by high-resolution LC-MS/MS analysis, quantitative global proteome analysis was performed. Results: In total, more than 3000 proteins were quantified and 34 proteins were found to be differentially expressed. The learning group was associated with increased expression of Calcium/Calmodulin-Dependent Protein Kinase II Delta (CAMK2D) which currently investigated phosphorylates HDAC5 and increases the activity of the MEF2 transcription factor, resulted in produces rapid antidepressant-like effect in animal assays for depression. Besides, our results indicate that increased expression of PSAP, GLB1, VDBP, TSPAN2 within the hippocampal regions could be part of a depression improvement mechanism. Conclusions: Chronic stress-induced depressive rats showed decreasing of neurons and dendritic spines in hippocampus. Spatial learning improved depressive symptoms and these studies have shown the key role of hippocampus in depression.