Electroacupuncture Ameliorates Depressive-Like Behaviors in Poststroke Rats via Activating the tPA/BDNF/TrkB Pathway

Abstract

Background Electroacupuncture (EA) is a form of physical therapy that has been widely used in clinical practice in China. Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke. EA has been shown to have beneficial effects on PSD patients. However, the potential mechanism underlying the protective effects of EA on PSD remains unclear. Here, we investigated whether tissue plasminogen activator (tPA)/brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling pathway participates in the therapeutic effects of EA in a rat PSD model. Methods Experimental PSD was induced by combining middle cerebral artery occlusion (MCAO) with chronic unpredictable mild stimulation (CUMS) in adult male rats. Bodyweight gain, neurological score, sucrose preference, and open field test were determined at 0, 7, 14, and 35 days after completing MCAO. The protein expressions of tPA, precursor BDNF (proBDNF), mature BDNF (mBDNF), and TrkB were measured by immunofluorescence and Western blot analysis. The tPA inhibitor plasminogen inhibitor-1 (PAI-1) was used to explore whether tPA plays a crucial role in the protective effects of EA on PSD. Results Compared with the sham rats, the PSD rats showed decreased bodyweight, deteriorated neurological score, and significant depressive-like behaviors. EA remarkably reversed bodyweight loss, neurological deficit, and depressive-like behaviors in PSD rats. Immunofluorescence staining and Western blot analysis showed that PSD-induced decreased expression of tPA, mBDNF, and TrkB were prevented by EA. Furthermore, we found that the effects of EA against PSD-induced depressive-like behaviors were abolished by PAI-1, the specific inhibitor of tPA. Conclusion Our results suggest that the improvement in depressive-like behaviors induced by EA is likely achieved via activation of the tPA/BDNF/TrkB pathway.

Global trends and hotspots in research on acupuncture for stroke: a bibliometric and visualization analysis

“…The mechanism of action [ 52 ] may be related to the activation of the expression of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB) gene. The improvement of depression by EA may be achieved by activating the tissue plasminogen activator (tPA)/BDNF/TrkB pathway [ 53 ]. EA attenuates cognitive impairment in stroke rats by regulating endogenous melatonin secretion through synthesizing the aralkylamine N-acetyltransferase gene in the pineal gland.…”

Evaluation of electroacupuncture as a non-pharmacological therapy for astrocytic structural aberrations and behavioral deficits in a post-ischemic depression model in mice

“…Indeed, a recent systematic review and meta-analysis by Li et al (2022) summarized that Chinese herbal medicine (CHM), another important component of traditional Chinese medicine, showed significant improvement in depressive-like behaviors and neurological function of post-stroke depression animals by regulating neurotrophic factors, hormones, and corresponding signaling cascades in regulating neuroinflammatory responses and promoting hippocampal neuron regeneration. However, in contrast, only limited research has recently investigated the antidepressant effect of EA in laboratory animals with PID ( Guilloux et al, 2011 ; Cai et al, 2019 ; Dong et al, 2021 ). Our data may provide a basis for future studies of acupoint selection and behavioral analysis in the PID condition.…”

Inflammatory Pathogenesis of Post-stroke Depression

“…In a rat model of PSD, serum levels of proBDNF are significantly increased in PSD rats, with a marked decrease in the ratio of mBDNF to proBDNF. The increase in proBDNF and the decrease in mBDNF are related and this imbalance may lead to a decline in hippocampal neural functions, thereby promoting the development of PSD [148].…”