Qi Li, Liang Wang, Xin-Yi Li, Xiao Chen, Bin Lu, Long Cheng, Chao-Gan Yan, Yong Xu
Abstract
We investigated the therapeutic effects and underlying brain functional network topology mechanisms of total salvianolic acid (TSA) treatment for memory dysfunction by using miR-30e overexpression-induced memory deficit in rat hippocampi. Model rats were developed by lentivirus vectors carrying miR-30e into bilateral hippocampus CA1 region through stereo-surgery. Two weeks after surgery, TSA (20 or 10 mg/mL/kg) or saline were administrated for 14 consecutive days. Memory function was assessed by behavioral tests (Y maze and Morris water maze [MWM]); resting-state functional MRI (RS-fMRI); and molecular alterations of BCL-2, UBC9, and Caspase-3 in the hippocampus CA1 region, as detected by immunohistochemistry. Compared to controls, model rats exhibited significantly impaired working and long-term memory in the Y maze and MWM tests (p < 0.01). The brain functional network topology analyzed based on RS-fMRI data demonstrated that miR-30e disturbed the global integration and segregation balance of the brain (p < 0.01), and reduced edge strength between CA1 and the posterior cingulate, temporal lobe, and thalamus (p < 0.05, false discovery rate corrected). At the molecular level, BCL-2 and UBC9 were downregulated, while Caspase-3 was upregulated (p < 0.01). After TSA (20 mg/mL/kg) treatment, the biomarkers for behavioral performance, global integration and segregation, edge strength, and expression levels of BCL-2, UBC9, and Caspase3 returned to normal levels. The correlation analyses of these results showed that global brain functional network topologic parameters can be intermediate biomarkers correlated with both behavioral changes and molecular alterations. This indicated that the effects of TSA were achieved by inhibiting apoptosis of CA1 neurons to improve global functional network topology.
Pharmacology, Toxicology and Pharmaceutical Science
1
5%
Other
4
19%
Unknown
8
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 July 2018.
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#22,767,715
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Outputs from Frontiers in Neuroscience
#10,138
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#299,003
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Outputs of similar age from Frontiers in Neuroscience
#228
of 235 outputs
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