Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

Antidepressant effects of acupuncture in a murine model: regulation of neurotrophic factors.

BACKGROUND: GV20 and Yintang are important targets in acupuncture treatment for depression. In this study, we examined the antidepressant effects of simultaneous acupuncture stimulation at GV20 and Yintang. METHODS: We compared the antidepressant effects of manual acupuncture (MA) stimulation at GV20 and Yintang, compared to acupuncture stimulation at two control point locations on the back of the mice (overlying the spinal column) and imipramine administration in a forced swimming (FS)-induced mouse model of depression, and examined the mRNA and protein expression of neurotrophic factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3, and NT-4/5 in the brains by real-time polymerase chain reaction in two different experimental schedules - preventive (MA given alongside FS modelling) and therapeutic (MA given after FS-induced depression was already established). RESULTS: MA at GV20 and Yintang significantly reduced the immobility time of mice with FS-induced depression in both preventive and therapeutic experimental designs, with effects that were comparable to those of imipramine administration. Immobility time following simultaneous acupuncture stimulation of the two control point locations overlying the spinal column was significantly suppressed only 2 weeks after the start of FS in the preventive effect experiment, and the suppressive effect was significantly lower than that of simultaneous acupuncture stimulation at GV20 and Yintang. In the therapeutic effect experiment, there was no change in the increase in immobility time after the end of FS. MA at GV20 and Yintang significantly increased the expression of BDNF and NT-3 in the preventive evaluation and NGF, BDNF, NT-3, and NT-4/5 in the therapeutic effect evaluation. CONCLUSION: Our findings suggest that simultaneous acupuncture stimulation at GV20 and Yintang is effective for the prevention and treatment of depression, and the effect likely involves modulation of the expression of multiple neurotrophic factors.

Electroacupuncture-modulated extracellular ATP levels in prefrontal cortex ameliorated depressive-like behavior of maternal separation rats.

Maternal separation (MS) is a type of early-life stress that has been linked to neuropsychiatric disorders, especially depression. Increasing evidence indicates that the adenosine triphosphate (ATP) level in the prefrontal cortex (PFC) is involved in the pathophysiology of depression. To investigate the potential relationship between ATP in PFC and antidepressant effects of electroacupuncture (EA) treatment, we assessed genes involved in ATP biosynthesis as well as the extracellular ATP levels in a rat model exposed to neonatal MS. Our results demonstrated that reduced expression of ABCG2 (an ATP-binding cassette protein) and ATP levels in the PFC of depressive-like rats exposed to MS can be attenuated by EA stimulus at the Baihui (GV20) and Yintang (GV29) acupoints. Moreover, the antidepressant effect of EA treatment was blocked by administration of suramin, a broad purinergic P2 receptor antagonist. Together, these results suggested that electroacupuncture may be able to modulate extracellular ATP levels in the PFC of depressive-like MS rats, potentially contributing to its antidepressant effects.

Electroacupuncture Alleviates Depressive-like Behavior by Modulating the Expression of P2X7/NLRP3/IL-1ß of Prefrontal Cortex and Liver in Rats Exposed to Chronic Unpredictable Mild Stress.

Depression is a complex clinical disorder associated with poor outcomes. Electroacupuncture (EA) has been demonstrated to have an important role in both clinical and pre-clinical depression investigations. Evidence has suggested that the P2X7 receptor (P2X7R), NLRP3, and IL-1ß play an important role in depressive disorder. Our study is aimed at exploring the role of EA in alleviating depression-like behaviors in rats. We therefore investigated the effects of EA on the prefrontal cortex and liver of rats subjected to chronic unpredictable mild stress (CUMS) through behavior tests, transmission electron microscopy, Nissl staining, HE staining, immunohistochemistry and Western blotting. Five weeks after exposure to CUMS, Sprague-Dawley (SD) rats showed depression-like behavior. Three weeks after treatment with brilliant blue G (BBG) or EA, depressive symptoms were significantly improved. Liver cells and microglia showed regular morphology and orderly arrangement in the BBG and EA groups compared with the CUMS group. Here we show that EA downregulated P2X7R/NLRP3/IL-1ß expression and relieved depression-like behavior. In summary, our findings demonstrated the efficacy of EA in alleviating depression-like behaviors induced by CUMS in rats. This suggests that EA may serve as an adjunctive therapy in clinical practice, and that P2X7R may be a promising target for EA intervention on the liver-brain axis in treatment of depression.

Managing terminal restlessness, anxiety, and distress during the dying process with Yintang (EX-HN 3) point acupuncture or acupressure: a case series of 19 palliative care patients from a hospital in Germany.

This is a case series report of 19 palliative care patients where 23 acupuncture sessions were performed which included Yintang (EX-HN 3) acupuncture or acupressure for the relief of terminal restlessness, anxiety or psychological distress present during the dying process. There was an observable relief from the restlessness, anxiety and distress both in sessions where only Yintang (EX-HN 3) point acupuncture or acupressure was performed (observed in 10 out of 11 sessions) as well as in sessions where Yintang (EX-HN 3) point acupuncture or acupressure was performed together with additional interventions, such as other points acupuncture, ear acupuncture or benzodiazepine treatment (observed in 10 out of 12 sessions). In total relief was observed in 20 out of 23 sessions (86.9%). A hypothesis that might worth further testing is whether Yintang (EX-HN 3) acupuncture or acupressure has an anxiolytic, tranquillising or sedative effect in dying patients. If confirmed this could be potentially useful in the fields of palliative care or disaster/triage medicine.

[Effects of Xiusanzhen treatment on ultrastructure of olfactory bulb and GFAP expression in mice with Parkinson's disease].

OBJECTIVE: To observe the effects of Xiusanzhen treatment on the ultrastructure of olfactory bulb and the expression of substantia nigra glial fibrillary acidic protein (GFAP) in mice with Parkinson's disease (PD) induced by lipopolysaccharide (LPS), and to provide methods and evidence for early prevention and treatment of PD. METHODS: Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method. RESULTS: ① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all P<0.05). The results of behavioristics test indicated footprint length and swimming time in the model group, the EA group and medication group was significantly lower than those in the blank group (all P<0.01), indicating the successful establishment of PD model. ② After one-session treatment, the symptoms of quiver and fear of chill were not observed in the EA group. After 4-session treatment, the BMI in the EA group was significantly higher than that in the model group (P<0.05); the symptoms of quiver and fear of chill were not observed in the medication group, but the BMI was similar with the model group (P>0.05). ③ After treatment, the footprint and swimming time in the model group were significantly lower than that in the blank group (both P<0.01); the footprint and swimming time in the EA group and medication group were significantly higher than those in the model group (all P<0.01).④ After treatment, compared with the blank group, the organelles and ultrastructure of olfactory bulb in the model group were significantly improved; the ultrastructure of olfactory bulb in the EA group was improved compared with that in the model group. ⑤ After treatment, the expression of substantia nigra GFAP in the model group was significantly higher than that in the blank group (P<0.01); the expression of substantia nigra GFAP in the EA group and medication group was significantly lower than that in the model group (both P<0.05). CONCLUSION: The early treatment of Xiusanzhen can improve behavioral disorders in LPS-induced early PD mice, and the mechanism may be related to the regulation of olfactory disorders and the expression of GFAP in substantia nigra.

Effect of Manual Acupuncture Stimulation at "Bai-Hui" (GV 20) or "Yintáng" (Ex-HN3) on Depressed Rats.

A previous study on rats showed that simultaneous acupuncture stimulation at the "Bai-Hui" (GV 20) and the "Yintáng" (Ex-HN3) acupoints alleviated the state of depression to an extent similar to that achieved by pharmacotherapy. This study investigated whether the alleviation of the depressed state required simultaneous acupuncture at these two acupuncture points. For the purposes of testing the effect of acupuncture on depressive symptoms, we treated a depression model rat, where depression had been induced by using a mild water-immersion stress technique, with either acupuncture stimulation at only one acupuncture point (GV 20 or Ex-HN3) or an antidepressant, and we measured the immobile time for evaluating the state of depression. Anxiety, as a symptom commonly associated with depression, was also evaluated by measuring the number of head dips. Neither the immobile time nor the number of head dips decreased upon acupuncture stimulation. From this study, single acupuncture stimulation at either "GV 20" or "Ex-HN3" alleviated neither the state of depression nor the anxiety. The water-immersion stress used to make the depression model rats was shown not to induce anxiety; however, the stress induced by immobilizing the rats for acupuncture stimulation did lead to anxiety.

Effects of Acupuncture at the Yintang and the Chengjiang Acupoints on Cardiac Arrhythmias and Neurocardiogenic Syncope in Emergency First Aid.

This study evaluated the effectiveness of YinTang and ChengJiang acupoints on patients with cardiac arrhythmia and neurocardiogenic syncope in emergency first aid. A 45 year old woman underwent acupuncture. She had a previous history of a valvuloplasty for rheumatic disease and two acute myocardial infarctions, followed by four catheterizations and an angioplasty. Needling of the YinTang acupoint and stimulation of the ChengJiang acupoint through acupressure were performed for 20 minutes soon after syncope and during tachycardia, hypertension, tachypnea, and precordial pain, without any effect on peripheral oxygen saturation (SpO2) or the glycemic index. Data were analyzed comparatively by using the following parameters at rest, during syncope, and at 1 minute and 10 minutes after an emergency acupuncture procedure: blood pressure; heart rate; SpO2; and respiratory rate. We found that acupuncture at YinTang and ChenJiang acupoints induced cardiovascular responses, increased the limits of the body's homeostasis, and normalized the patient's condition in the case of syncope. Acupuncture using a combination of ChengJiang and YinTang acupoints had an immediate effect on the autonomic nervous system and on maintaining homeostasis and energy balance in the body. Although this technique was effective, the patient was still referred to the Emergency Room.

Effect of acupuncture stimulation on rats with depression induced by water-immersion stress.

Depression is a kind of mood disorder. The incidence of depressed patients has demonstrated an upward trend in recent years. Symptoms may improve with treatments such as pharmacotherapy and cognitive-behavioral therapy, but such approaches may exert strong side effects, and therapeutic effects can be slow. We studied how acupuncture stimulation would affect depression as a method to reduce side effects. Mild depression was induced in rats by 1-week water-immersion stress. We treated these mildly depressed rats with either acupuncture stimulation at the "Bai-Hui" (GV 20) and "Yintáng" (Ex-HN3) points, or antidepressants. We then measured the immobile time and serum corticosterone level in rats. Immobile time and serum corticosterone level decreased on stimulation with acupuncture or antidepressants. These findings suggest that mild depression in rats was improved by stimulation with acupuncture The mechanisms underlying such improvement may effect HPA system activated by this stress, and inhibit the response to lead to the disorder of the hippocampal nerve cell.

[Improvement of life quality of patients with allergic rhinitis treated with acupuncture on sphenopa-latine ganglion:a randomized controlled trial].

OBJECTIVE: To compare the effects of acupuncture on sphenopalatine ganglion and acupuncture on the common acupoints for life quality of patients with allergic rhinitis(AR). METHODS: Eighty patients with AR,who were in accord with the inclusive criteria,were randomly divided into an observation group and a control group,40 cases in each one. Acupuncture on sphenopalatine ganglion was used in the observation group. The needle was inserted into the gap between zygoma and mandibular coronoid process about 55 mm. Acupuncture was adopted on the main acupoints,Yingxiang(LI 20),Yintang(GV 29) or Fengchi(GB 20) in the control group. The course was four weeks. Follow-up was applied one month after treatment. Rhinoconjunctivitis quality of life questionnaire (RQLQ),rhinitis symptoms scale and visual analogue scale(VAS) were evaluated at different time points before and after treatment,and follow-up was implemented to know the recurrence situation,satisfactory degree and adverse reaction. RESULTS: (1) RQLQ scores:along with treatment,the RQLQ scores were gradually apparently decreased in the two groups(P<0.01),and the reducing trend from the first week to the second week of the observation group was more obvious than that of the control group. The differences of the RQLQ scores at all timepoints after treatment between the two groups were not statistically significant(all P>0.05). The interaction of the time factor and the group factor had statistical significance(P<0.01). (2) Rhinitis symptoms scores:along with treatment,the scores presented decreasing trend in the two groups(P<0.01). The scores of the two groups after treatment and the interaction of the time factor and the group factor were not statistically different(both P>0.05). (3)VAS scores:the VAS scores after treatment were lower than those before treatment(both P<0.01). The differences before and after treatment were statistically significant(P<0.01),with more change in the observation group(P<0.05). (4)There was no statistical significance about the number of recurrence days between the two groups(P>0.05). (5) Above 80 percent patients were content with the therapeutic method in each group,with no statistical difference(P>0.05). (6)The method of the observation group spent less time. (7) Two patients with light adverse reaction came up in the observation group,but no special treatment was needed. CONCLUSIONS: Acupuncture on sphenopalatine ganglion acquires more obvious short-term effect than conventional acupuncture. It spends less time to relieve symptoms and improves life quality.

Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints.

Preliminary basic research and clinical findings have demonstrated that electroacupuncture therapy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depression-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, Igf2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to normalize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.