Total Salvianolic Acid Balances Brain Functional Network Topology in Rat Hippocampi Overexpressing miR-30e

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.

KangPiLao decoction modulates cognitive and emotional disorders in rats with central fatigue through the GABA/Glu pathway

“…The MWM is a test of spatial learning and long-term memory for rats that utilizes distal cues to locate a submerged escape platform around the perimeter of an open swimming arena (Vorhees and Williams, 2006;D'Hooge and De Deyn, 2001). A circular tank (150 cm in diameter and 50 cm in depth) with a removable hidden platform (9 cm in diameter) submerged about 2 cm below the surface of the water (24 ± 1 °C) served as the apparatus (Li et al, 2018). To provide location cues, different marker colors and shapes were placed, and each rat was trained four times for four consecutive days.…”

Simultaneous determination of 19 constituents in the Jian‐Nao‐Ning mixture using high‐performance liquid chromatography‐tandem mass spectrometry

“…In general, the inter-batch differences of the contents of several JNNm major constituents including salvianolic acid B, betaine, and lobetyolin were within 10%. It was reported that total salvianolic acid improved brain function in rats by inhibiting apoptosis of CA1 neurons to improve global functional network topology [19]. Furthermore, spinosin has anxiolytic, sedative, and hypnotic effects [20].…”

“…It was reported that total salvianolic acid improved brain function in rats by inhibiting apoptosis of CA1 neurons to improve global functional network topology [19]. Furthermore, spinosin has anxiolytic, sedative, and hypnotic effects [20].…”

Peanut meal extract fermented with Bacillus natto attenuates physiological and behavioural deficits in a d-galactose-induced ageing rat model

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