Abstract
ObjectiveUsing a rat model of chronic unpredictable mild stress (CUMS), to investigate the effects of electroacupuncture (EA) on the tissue plasminogen activator (tPA)/brain-derived neurotrophic factor (BDNF) pathway.MethodsSixty male Sprague–Dawley rats were randomly divided into four groups: normal, model, fluoxetine (fluox), or EA. Experimental groups were subjected to 28 d of CUMS modeling. One hour after CUMS, the fluox and EA groups were treated with fluox and a 20 min EA intervention, respectively. Depressive-like behaviors were assessed by open field and sucrose preference tests. After the rats were sacrificed, brains were dissected and processed using hematoxylin and eosin (HE) staining to observe changes in the morphology and quantity of neurons in the hippocampal cornu ammonis 3 area. Western blot and real-time polymerase chain reaction (PCR) demonstrated the effects of EA on the tPA/BDNF pathway-related molecules in the hippocampi and raphe nuclei.ResultsCompared to the model group, the number of horizontal and vertical movements and the percentage of sucrose consumption in the EA groups were significantly increased (P < 0.01). Compared to the model group, HE staining showed that the hippocampal neurons in the EA and fluox groups were arranged neatly, with rich layers and complete cell structures. The Western blot and real-time PCR showed that the levels of tPA, BDNF, tropomyosin receptor kinase B, and BDNF micro RNA (mRNA) in the hippocampi of the EA group were higher than in the model group (P < 0.01, P < 0.01, P < 0.05, P < 0.01, respectively). The content of p75NTR, proBDNF, and tPA mRNA in the hippocampi of the EA group displayed no significant differences compared to the model group. The tPA mRNA content in the raphe nuclei of the EA group was higher than in the model group (P < 0.01), and the BDNF content in the raphe nuclei was lower than in the model group (P < 0.05). There were no significant differences in tPA and BDNF mRNA between the EA and model groups.ConclusionEA may reverse depressive-like behaviors in CUMS, which may be related to the tPA/BDNF pathway in the hippocampus.
Highlights
Depression is a common mental illness that is primarily associated with persistent mood dysfunction and is one of the leading causes of disability worldwide [1]
We investigated the effects of EA on tPA/BDNF pathway-related molecules in the hippocampus and raphe nuclei to better understand its mechanisms in the treatment of depression, thereby helping provide a theoretical basis for the clinical application of EA
The open field test (OFT) evaluated changes in autonomy and curiosity behaviors in rats, while the sucrose preference test (SPT) evaluated the degree of anhedonia
Summary
Depression is a common mental illness that is primarily associated with persistent mood dysfunction and is one of the leading causes of disability worldwide [1]. Acupuncture has been considered effective in the treatment of depression as it alleviates depressive symptoms in rats who have experienced maternal separation. Electroacupuncture (EA) has immediate and short-term effects in alleviating chronic pain, autonomic dysfunction, and mood disorder symptoms by modulating a distributed network of brain areas [5, 6]. Previous studies have found that impairments to the raphe nuclei have been found in patients with varying severities of depression using transcranial sonography and the structure’s echogenicity in patients with unipolar depression is typically lower than patients with Parkinson’s disease or healthy controls [8, 9]. While the underlying etiology and pathophysiology of depression remains unclear, these studies suggest that changes to the neurons in the hippocampus and raphe nuclei are important in the development and treatment of depression
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