Altered frequency-specific/universal amplitude characteristics of spontaneous brain oscillations in patients with bipolar disorder.

The human brain is a dynamic system with intrinsic oscillations in spontaneous neural activity. Whether the dynamic characteristics of these spontaneous oscillations are differentially altered across different frequency bands in patients with bipolar disorder (BD) remains unclear. This study recruited 65 patients with BD and 85 healthy controls (HCs). The entire frequency range of resting-state fMRI data was decomposed into four frequency intervals. Two-way repeated-measures ANCOVA was employed to detect frequency-specific/universal alterations in the dynamic oscillation amplitude in BD. The patients were then divided into two subgroups according to their mood states to explore whether these alterations were independent of their mood states. Finally, other window sizes, step sizes, and window types were tested to replicate all analyses. Frequency-specific abnormality of the dynamic oscillation amplitude was detected within the posterior medial parietal cortex (centered at the precuneus extending to the posterior cingulate cortex). This specific profile indicates decreased amplitudes in the lower frequency bands (slow-5/4) and no amplitude changes in the higher frequency bands (slow-3/2) compared with HCs. Frequency-universal abnormalities of the dynamic oscillation amplitude were also detectable, indicating increased amplitudes in the thalamus and left cerebellum anterior lobe but decreased amplitudes in the medial superior frontal gyrus. These alterations were independent of the patients' mood states and replicable across multiple analytic and parametric settings. In short, frequency-specific/universal amplitude characteristics of spontaneous oscillations were observed in patients with BD. These abnormal characteristics have important implications for specific functional changes in BD from multiple frequency and dynamic perspectives.

Capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption by blocking TRPV4 channels in healthy and colitic mice.

Although capsaicin has been studied extensively as an activator of the transient receptor potential vanilloid cation channel subtype 1 (TRPV1) channels in sensory neurons, little is known about its TRPV1-independent actions in gastrointestinal health and disease. Here, we aimed to investigate the pharmacological actions of capsaicin as a food additive and medication on intestinal ion transporters in mouse models of ulcerative colitis (UC). The short-circuit current (Isc) of the intestine from WT, TRPV1-, and TRPV4-KO mice were measured in Ussing chambers, and Ca2+ imaging was performed on small intestinal epithelial cells. We also performed Western blots, immunohistochemistry, and immunofluorescence on intestinal epithelial cells and on intestinal tissues following UC induction with dextran sodium sulfate. We found that capsaicin did not affect basal intestinal Isc but significantly inhibited carbachol- and caffeine-induced intestinal Isc in WT mice. Capsaicin similarly inhibited the intestinal Isc in TRPV1 KO mice, but this inhibition was absent in TRPV4 KO mice. We also determined that Ca2+ influx via TRPV4 was required for cholinergic signaling-mediated intestinal anion secretion, which was inhibited by capsaicin. Moreover, the glucose-induced jejunal Iscvia Na+/glucose cotransporter was suppressed by TRPV4 activation, which could be relieved by capsaicin. Capsaicin also stimulated ouabain- and amiloride-sensitive colonic Isc. Finally, we found that dietary capsaicin ameliorated the UC phenotype, suppressed hyperaction of TRPV4 channels, and rescued the reduced ouabain- and amiloride-sensitive Isc. We therefore conclude that capsaicin inhibits intestinal Cl- secretion and promotes Na+ absorption predominantly by blocking TRPV4 channels to exert its beneficial anti-colitic action.

Cyclopiazonic Acid-Induced Ca2+ Store Depletion Initiates Endothelium-Dependent Hyperpolarization-Mediated Vasorelaxation of Mesenteric Arteries in Healthy and Colitis Mice.

Purposes: Since the role of store-operated calcium entry (SOCE) in endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of mesenteric arteries in health and colitis is not fully understood, cyclopiazonic acid (CPA), a specific inhibitor of the sarco(endo) plasmic reticulum calcium-ATPases (SERCA), was used as a SOCE activator to investigate its role in normal mice and its alteration in colitis mice. Methods: The changes in Ca2+ signaling in vascular endothelial cells (VEC) were examined by single cell Ca2+ imaging and tension of mesenteric arteries in response to CPA were examined using Danish DMT520A microvascular measuring system. Results: CPA activated the SOCE through depletion of the endoplasmic reticulum (ER) Ca2+ in endothelial cells. CPA had a concentration-dependent vasorelaxing effect in endothelium-intact mesenteric arteries, which was lost after endothelial removal. Both nitric oxide (NO) and prostacyclin (PGI2) inhibitors did not affect CPA-induced vasorelaxation; however, after both NO and PGI2 were inhibited, KCa channel blocker [10 mM tetraethylammonium chloride (TEA)] inhibited CPA-induced vasorelaxation while KCa channel activator (0.3 µM SKA-31) promoted it. Two SOCE blockers [30 µM SKF96365 and 100 µM flufenamic acid (FFA)], and an Orai channel blocker (30 µM GSK-7975A) inhibited this vasorelaxation. The inhibition of both Na+/K+-ATPase (NKA) and Na+/Ca2+-exchange (NCX) also inhibited CPA-induced vasorelaxation. Finally, the CPA involved in EDH-induced vasorelaxation by the depletion of ER Ca2+ of mesenteric arteries was impaired in colitis mice. Conclusion: Depletion of ER Ca2+ by CPA induces a vasorelaxation of mesenteric arteries that is mediated through EDH mechanism and invokes the activation of SOCE. The CPA-induced endothelium-dependent dilation is impaired in colitis which may limit blood perfusion to the intestinal mucosa.

[Association of the tagging single nucleotide polymorphisms in transforming growth factor beta-1 gene with hypertension in the Han nationality population in Xinjiang].

OBJECTIVE: Essential hypertension (EH) was a complex disease resulted from the interaction of cumulative effect of multiple genetic and environment factors. The relationship between the genetic polymorphisms in the transforming growth factor-beta1 (TGF-beta1), the blood levels and EH have been investigated, but the conclusions were different. Therefore, we investigate the relationship between the tagging single nucleotide polymorphisms (tSNPs) (rs1800469, rs2241716, rs11466345, rs2241715, rs4803455) in TGF-beta1 gene, blood levels and EH in the Han nationality population in Xinjiang, to clarity the pattern of linkage disequilibrium (LD) and the feature of the structure of haplotype. METHODS: Based on the case-control study,we selected 732 (365 EH patients,367 controls) Han Chinese population from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China by random cluster sampling. After questionnaire and physical examination, we collected blood samples, and the blood levels of TGF-beta1 were quantified using sandwich ELISA. The polymorphisms of TGF-beta1 gene in the study groups were detected with SNaPshot system. The case-control study in a large group was carried out separately for each of the tSNP and followed up by haplotypes analyses to determine the relation between tSNPs of TGF-beta1 gene and EH in the Han population. RESULTS: (1) The frequencies of alleles A, G of rs11466345 of TGF-beta1 gene in EH group and control group were as follows: 69.7%, 30.3%, 74.4%, 25.6%, respectively. It was demonstrated that the G allele of the rs11466345 polymorphism occurred at a significantly higher frequency in EH patients than in healthy controls (30.3% vs. 25.6%, P < 0.05). The rs11466345G-allele carriers had a significantly increased risk of EH compared to rs11466345A-allele carrier (OR = 1.261; P < 0.05). The frequencies of genotypes and alleles of the other tSNPs of TGF-beta1 gene had no difference between EH patients and controls (P > 0.05). (2)Except the site of rs11466345, the other tSNPs were in strong LD, and no statistical differences were observed in haplotypes distribution in the followup study between case-control groups (P > 0.05). (3) There were no difference of TGF-beta1 levels between the different genotypes and alleles in tSNPs of TGF-beta1 gene (P > 0.05). CONCLUSIONS: (1) These results suggested that TGF-beta1 gene rs11466345 G allele was likely to be a genetic susceptibility factor for EH in the Xinjiang Han population, the other tSNPs perhaps had no association with EH of in the study groups. (2) Except rs11466345, the other tSNPs were in strong LD, and the haplotypes reconstructed by tSNPs might not be associated with EH in the Han nationality populations. (3) There was no association between the tSNP of TGF-beta1 gene and TGF-beta1 blood levels in the Xinjiang Han nationality population.