Jiedu Tongluo Granules Ameliorates Post-stroke Depression Rat Model via Regulating NMDAR/BDNF Signaling Pathway

Abstract

Post-stroke depression (PSD) is one of the most common stroke complications, which seriously affects stroke’s therapeutic effect and brings great pain for patients. The pathological mechanism of PSD has not been revealed. Jiedu Tongluo granules (JDTLG) is an effective traditional Chinese medicine for PSD treatment which is widely used in clinical treatment. JDTLG has a significant therapeutic effect against PSD, but the mechanism is still unclear. The PSD rat model was established by carotid artery embolization combined with chronic sleep deprivation followed by treating with JDTLG. Neurobehavioral and neurofunctional experiments were engaged in studying the neural function of rats. Histomorphology, proteomics, and western blotting researches were performed to investigate the potential molecular mechanisms related to JDTLG therapy. Oral treatment of JDTLG could significantly improve the symptoms of neurological deficit and depression symptoms of PSD rats. Proteomic analysis identified several processes that may involve the regulation of JDTLG on the PSD animal model, including energy metabolism, nervous system, and N-methyl-D-aspartate receptor (NMDAR)/brain-derived neurotrophic factor (BDNF) signal pathway. Our results showed that JDTLG could reduce glutamate (Glu) level and increase gamma-aminobutyric acid (GABA) level via regulating the NMDAR/BDNF pathway, which may play a vital role in the occurrence and development of PSD.

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

“…Then, 50 μg of protein from each sample was loaded onto an SDS-PAGE gel of 10%-12% and electroblotted onto polyvinylidene fluoride (PVDF) membranes. After blocking the PVDF membranes with 4% skim milk in Tris-Buffered Saline and Tween (TBST) buffer for 1 h (Zhao et al, 2021), the following antibodies were incubated overnight at 4 °C with the membranes: NMDAR2B (1:2000; Proteintech), GABABR1 (1:1,000; Abcam), GAT-1 (1:500; Abcam), GAD67 (1:1,000; Proteintech), GABAARα1 (1:2,000; Proteintech), GAGAARγ2 (1:1,000; Proteintech), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) (1:10,000, Proteintech). The membranes were then incubated with secondary antibodies (goat anti-rabbit IgG or goat anti-mouse IgG) for 2 h and washed thrice.…”

Bioinformatic prediction of depression-related signaling pathways regulated by miR-146a in peripheral blood of patients with post-stroke depression

“…Brain tissue damage occurs in patients after stroke, which may damage the emotional center (14). The reduction of the biochemical transmitter 5-HT and norepinephrine in brain tissues can lead to depression, and the blockade of nerve conduction pathways can also make patients in low spirits (15). Depression will hinder the recovery of neurological functions in stroke patients; in severe cases, the patient's ability to live and quality of life will be affected, even it will cause death (16).…”

Combination of panax ginseng and ginkgo biloba extracts attenuate cerebral ischemia injury with modulation of NLRP3 inflammasome and CAMK4/CREB pathway

“…Rats were sacrificed after deep anesthetization. Brain tissues were fixed in 4% paraformaldehyde at 4°C for 24 h, dehydrated in gradient alcohols, then embedded in paraffin, and cut into 5 µm thick sections ( Zhao et al, 2021 ). The sections were stained with HE and assessed by a light microscope (Olympus FV1200, Tokyo, Japan).…”