total salvianolic acid balances brain functional network topology in rat hippocampi overexpressing mir-30e

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ID: 154656
2018
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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.
Reference Key
li2018frontierstotal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Qi Li;Liang Wang;Liang Wang;Xin-Yi Li;Xiao Chen;Bin Lu;Long Cheng;Chao-Gan Yan;Yong Xu;Yong Xu;Yong Xu
Journal Journal of enzyme inhibition and medicinal chemistry
Year 2018
DOI
10.3389/fnins.2018.00448
URL
https://www.frontiersin.org/article/10.3389/fnins.2018.00448/full
Keywords
graph theory rs-fmri neuropsychiatry biological psychiatry

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