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 Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS: EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

[Exploration of the correlation between Chinese medicine syndrome types of verrucous gastritis and the pressions of gastric mucosal hypoxia-inducible factor-1alpha as well as downstream molecules].

OBJECTIVE: To study the expressions changes of gastric mucosal hypoxia-inducible factor-1alpha (HIF-1alpha) and downstream molecules [such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2)] of verrucous gastritis (VG) patients of different Chinese medicine (CM) syndrome types and their clinical significance. METHODS: Totally 94 VG patients were assigned to Gan-Wei disharmony group (GWDG, 28 cases), the damp-heat in Pi-Wei group (DHPWG, 17 cases), the blood stasis in Wei-collateral group (BSWCG, 20 cases), and the insufficiency of Pi-yang group (IPYG, 29 cases). Another 30 patients with chronic mild non-active superficial gastritis patients accompanied with negative Hp infection were recruited as the control group. The Hp infection was detected using 14C-labeled urea breath test. The expressions of HIF-1alpha, VEGF, and COX-2 in the gastric mucosal tissue were detected using immunohistochemical EnVision two-step test. RESULTS: The positive Hp infection rate in VG patients was 37.23% (35/94 cases). The positive Hp infection rate in patients of DHPWG (76. 47%) was significantly higher than the other three groups (32.14% in GWDG, 31.03% in IPYG, and 20.00% in BSWCG, P < 0.01). The expressions of HIF-1alpha and COX-2 in VG patients of different syndrome types were obviously higher than those of the control group (P < 0.01, P < 0.05). Of them, the expression of HIF-1alpha was the highest in BSWCG and the expression of COX-2 was the highest in DHPWG. The expression of VEGF was higher in DHPWG and IPYG than in the control group and the GWDG (P < 0.01, P < 0.05). CONCLUSIONS: The expressions of HIF-1alpha, VEGF, COX-2, and Hp infection showed certain changes in VG patients of different syndrome types. The expression of HIF-1alpha was the strongest in BSWCG. The expressions of VEGF and COX-2 as well as Hp infection were the highest in DHPWG. All showed the specificity of CM syndromes.

[Orexin A and neuropeptide Y levels in plasma and hypothalamus of rats with chronic renal failure].

OBJECTIVE: To explore the changes of orexin A and neuropeptide (NPY) in plasma and hypothalamus of rats with chronic renal failure (CRF). METHODS: 41 male Wister rats weighing 200 approximately 250 g were randomly divided into three groups: normal group, sham operation group, and CRF group (with the right kidney and 2/3 of the left kidney resected). A certain number of rats were decapitated 4, 8,and 12 weeks after respectively. Their hypothalami were removed and blood collected. Radioimmunoassay was used to measure the levels of orexin A and NPY in hypothalamus and plasma. Automatic biochemical analyzer was used to measure the serum creatinine. RESULTS: The serum creatinine level of CRF rats was both significantly higher than those of the sham operation rats at week 8 and week 12, respectively. The plasma orexin A level of CRF rats at week 12 was 264 pg/ml +/- 62 pg/ml, significantly higher than that of sham operation group (183 pg/ml +/- 56pg/ml, P = 0.039). The hypothalamus orexin A level of CRF rats were 10.5 fmol/mg +/- 2.7 fmol/mg wet weight at week 12, significantly lower than that of sham operation rats (17.4 fmol/mg +/- 3.9 fmol/mg wet weight, P = 0.023). The plasma NPY levels of CRF rats at week 8 and week 12 were significantly higher than those of the sham operation rats (7.1 pmol/ml +/- 1.7 pmol/ml vs 5.0 pmol/ml +/- 0.5 pmol/ml, P = 0.01; and 7.9 pmol/ml +/- 1.1 pmol/ml vs 4.8 pmol/ml +/- 1.1 pmol/ml, P = 0.0008). The hypothalamus NPY level of CRF rats at week 12 were 70 fmol/mg +/- 23 fmol/mg wet weight, significantly lower than that of the sham operation rats (113 fmol/mg +/- 31 fmol/mg wet weight, P = 0.03). CONCLUSION: Loss of renal function may diminish the excretion of orexin A and neuropeptide. The lowering of hypothalamus orexin A and neuropeptide Y levels may be one of the causes inducing anorexia in CRF.