Chronic stress induces fur color change from dark to brown by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice / 生理学报

Increasing evidence suggests that stress may induce changes in hair color, with the underlying mechanism incompletely understood. In this study, female C57BL/6 mice subjected to electric foot shock combined with restraint stress were used to build chronic stress mouse model. The melanin contents and tyrosinase activity were measured in mouse skin and B16F10 melanoma cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor α (TNF-α), interleukin- 1β (IL-1β) and interleukin-6 (IL-6) in the mouse skin. The content of nuclear factor κB (NFκB)/p65 subunit in mouse skins was valued by immunofluorescence staining. The results demonstrated that under chronic stress, the fur color turned from dark to brown in C57BL/6 mice due to the decrease of follicle melanocytes and tyrosinase activity in C57BL/6 mouse skin. Simultaneously, inflammatory responses in skins were detected as shown by increased NFκB activity and TNF-α expression in stressed mouse skin. In cultured B16F10 melanoma cells, TNF-α reduced the melanogenesis and tyrosinase activity in a dose-dependent manner. These findings indicate that chronic stress induces fur color change by decreasing follicle melanocytes and tyrosinase activity in female C57BL/6 mice, and TNF-α may play an important role in stress-induced hair color change.

Inflammatory mechanism of depression and its new strategy for diagnosis and treatment / 生理学报

Depression is a major class of mental illness; owing to its high prevalence, high disability rate and heavy disease burden, it has become a stern and formidable global health problem. It is generally believed that the etiology of depression is multifactorial, which is related to gender differences, chronic stress, dietary behavior and drug abuse. At present, the exact pathophysiological mechanism of depression still remains unclear, but researchers across the globe put forward various hypotheses to interpret the possible access to this disease, including monoamine neurotransmitter disturbance, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, lack of neurotrophic factors and excessive pro-inflammatory cytokines. Based on the latest research evidence and the objective fact that traditional antidepressants may be ineffective in some particular patients, the "cytokine theory" tends to attract more and more attention recently. To date, researches on the role of cytokines in the pathogenesis of depression mainly focus on pro-inflammatory cytokines, especially categories including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). With the proceeding of researches from all over the world, a variety of novel molecules and mechanisms were postulated. This paper summarized a large amount of in vitro and in vivo research evidence, in order to review the current progress of the researches on pathophysiology of depression from the perspective of pro-inflammatory cytokines. Since the response rate of antidepressant therapy during present medical practice is unsatisfying, we suggest a new feasible diagnosis and treatment strategy, that is to distinguish the inflammatory status of patients with depression and take anti-inflammatory treatment into consideration. Totally, this novel strategy aims at modulating the conventional clinical protocol for treatment-resistant depressive patients and overcoming the limitation of insufficient antidepressant response possibly resulted from inflammation.

Roles of cytokines in stress-induced depression / 生理学报

Depression is a very common mental health problem in our modern society. Stress is involved in the provocation of depression. The pathogenesis of depressive disorder is still not well known. The development of neuroendocrine immunology opens a new sight for clarification of mechanism underlying stress-induced depression. Chronic stress activates peripheral and central immune systems accompanied with the release of inflammatory mediators, including cytokines. Activated immune system mediates the process of depression through the interaction with neuron system and neuroendocrine system, including regulating the monoamine neurotransmitter system in synthesis, metabolism and reuptake, inducing the overactivation of hypothalamus-pituitary-adrenal (HPA) axis and its negative feedback regulation, and reducing neurogenesis. This present paper reviews the cytokines mechanisms underlying stress-induced depression.

Tumor conditioned medium regulates the proliferation, adhesion and migration of human umbilical vein endothelial cells / 生理学报

The aim of the present study was to investigate the effects of tumor conditioned medium (TCM) on the proliferation, adhesion and migration of human umbilical vein endothelial cell (HUVEC). Cells were divided into control group, TCM stock solution group, TCM monodilution group and TCM didilution group (n = 6), and MTT assay was used to determine endothelial cells proliferation level after being stimulated with TCM for 24 h. Coating culture dishes with Fn was used to detect the adhesion ability of endothelial cells to basement membrane in control group and TCM stock solution group (n = 6). Wound closure model was used to test the migration ability of endothelial cells in control group and TCM stock solution group at 12 h and 24 h (n = 6). The results showed that TCM at different concentrations influenced proliferation of endothelial cells in distinct degree. Compared to the control group (absorbance value: 0.58 ± 0.04), the stock solution had no effect on proliferation of endothelial cells (absorbance value: 0.55 ± 0.01). However, the TCM monodilution and TCM didilution enhanced the proliferation of endothelial cells significantly (absorbance value: 0.66 ± 0.03, P < 0.01 and 0.70 ± 0.02, P < 0.001 separately). TCM downregulated the adhesion of endothelial cells to basement membrane. Moreover, compared to the migration distance of control group at 12 h and 24 h [(14.05 ± 6.25) µm and (48.75 ± 16.37) µm separately], TCM upregulated the basement membrane migration [(68.25 ± 26.20) µm and (119.70 ± 34.90) µm at 12 h and 24 h, both P < 0.05 separately]. These results suggest that TCM downregulates the adhesion ability of endothelial cells and upregulates their migration ability, and thus facilitates tumor metastasis.

Corticosterone rapidly promotes respiratory burst of mouse peritoneal macrophages via non-genomic mechanism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The immunomodulatory effects of glucocorticoids (GCs) have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immunosuppressive mechanisms of GCs have been investigated intensely, the immunopermissive effects of GCs remain unclear. A lot of studies showed GCs could exert rapid non-genomic actions. We herein studied the rapid immunopromoting effects of GCs.</p><p><b>METHODS</b>We observed the rapid (within 30 minutes) effects of corticosterone on respiratory burst of mouse peritoneal macrophages and studied their mechanisms. The superoxide anions were measured by cytochrome C reduction assay. Protein kinase C phosphorylation was measured by Western blotting and membrane fluidity was evaluated by fluorescence polarization measurement.</p><p><b>RESULTS</b>The 10(-8) mol/L and 10(-7) mol/L corticosterone rapidly increased the superoxide anions production by macrophages, which were insensitive to GC-receptor antagonist, mifepristone, and protein-synthesis inhibitor, cycloheximide. Corticosterone coupled to bovine serum albumin was able to mimic the effects of corticosterone. The effects were independent of protein kinase C pathway and the change in membrane fluidity.</p><p><b>CONCLUSIONS</b>The results indicate that corticosterone rapidly promote the superoxide anions production by mouse peritoneal macrophages may through non-genomic mechanisms. This study may contribute to understanding the effects of GCs under stress condition and the physiological significance of nongenomic effects of GCs.</p>

Rapid inhibitory effect of glucocorticoids on peak of Ca2+i and PLC in airway smooth muscle / 中国应用生理学杂志

<p><b>OBJECTIVE</b>In this study, we pretreated the mice ASMCs by dexamethasone (Dex) within 10 min, to test the peak of [Ca2+]i and phospho-PLCbeta (ser1105) in the cells by treated with Ach.</p><p><b>METHODS</b>The peak of [Ca2+]i was measured by Fura-2/AM methods and the phospho-PLCbeta-ser1105 was by Western blot, and compared with dexamethasone pretreated groups. Glucocorticoid receptor antagonist RU486 and the protein synthesis inhibitor cycloheximide groups were settled in our study.</p><p><b>RESULTS</b>Glucocorticoids (GCs) significantly decreased the resting values and peak of [Ca2+]i elevation and elevated the intracellular levels of phospho-PLCbeta (ser1105) in 10 min. Neither the RU486 nor cycloheximide could alter the inhibitory effects of glucocorticoids stated above.</p><p><b>CONCLUSION</b>Our results demonstrate that glucocorticoids exert rapid inhibitory effects. The series of signal changes in this process that restrain the peak of [Ca2+]i may be responsible for the rapid nongenomic inhibitory effects of GCs by reducing the activity of PLC.</p>

Neuropeptide Y promotes TGF-beta1 production in RAW264.7 cells by activating PI3K pathway via Y1 receptor / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To examine the effect of neuropeptide Y (NPY) on TGF-beta1 production in RAW264.7 macrophages.</p><p><b>METHODS</b>Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-beta1 production. Cell counting kit 8 (CCK-8) was used to assay the viability of RAW264.7 cells. Western blot was used to detect the phosphorylation of PI3K p85.</p><p><b>RESULTS</b>NPY treatment could promote TGF-beta1 production and rapid phosphorylation of PI3K p85 in RAW264.7 cells via Y1 receptor. The elevated TGF-beta1 production induced by NPY could be abolished by wortmannin pretreatment.</p><p><b>CONCLUSION</b>NPY may elicit TGF-beta1 production in RAW264.7 cells via Y1 receptor, and the activated PI3K pathway may account for this effect.</p>

The state of SHP-1 and CD45 in lymphocyte under high partial pressure of oxygen / 中国应用生理学杂志

<p><b>AIM</b>To explore the function state of protein tyrosine phosphatase (PTP) SHP-1 and CD45 under high partial pressure of oxygen (Po2) in lymphocyte.</p><p><b>METHODS</b>Primarily cultured rat splenic lymphocytes were treated with different pressure-duration of oxygen that led to promotion or inhibition of cell function. The catalytic activities, protein expression and tyrosine phosphorylation of SHP-1 and CD45 were determined.</p><p><b>RESULTS</b>The activity of SHP-1 was decreased after high Po2 treatment no matter what pressure-duration was, while the activity of CD45 was decreased only after high PoF that led to inhibition of lymphocyte function. The proteins expressed and tyrosine phosphorylation levels of two enzymes had no alteration in most treatment groups.</p><p><b>CONCLUSION</b>The decrease of PTP catalytic activities might be caused by their structures modification by high Po2 induced reactive oxygen species. SHP-1 and CD45 might be one of the key points of action through which high PO2 exerts its effects on lymphocytes.</p>

Influence of acetazolamide given intraperitoneally on the latency to hyperbaric oxygen-induced convulsion of rats / 生理学报

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide or (and) indomethacin on the latency of hyperbaric oxygen-induced convulsion was observed. Seventy Sprague-Dawley (SD) rats were randomly divided into 7 groups: the acetazolamide 200, 20, 10, 7.5, 5, 2.5 mg/kg body weight and normal saline (NS) group. Forty rats were divided into 5 groups: indomethacin 20, 10, 5, 2.5 mg/kg body weight and NS groups. Another 40 rats were divided into 5 groups which were administered with indomethacin in the dose of 0 mg/kg (NS), 0 mg/kg (NS), 5, 10 and 20 mg/kg body weight. Thirty min later the first group was given NS, and all the other four groups were given acetazolamide with a dose of 7.5 mg/kg body weight. The animals were given acetazolamide or (and) indomethacin intraperitoneally, and 20 min later they were exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the change of maleic dialdehyde (MDA) was measured after acetazolamide and (or) indomethacin treatment. Seventy-two SD rats were randomly divided into 9 groups: Control, 6 and 16 min respectively with NS, acetazolamide, indomethacin, and both acetazolamide and indomethacin group. The dose of acetazolamide was 7.5 mg/kg body weight and the dose of indomethacin was 20 mg/kg body weight. After injection of drugs, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. Then the rats were decapitated and the cerebral cortex was dissected and homogenized. The content of MDA was determined. We found that (1) when the dose of acetazolamide is higher than 7.5 mg/kg, it shortened the latency to hyperbaric oxygen-induced convulsion significantly (P<0.05, P<0.01). There was no significant difference in the latency between every to hyperbaric oxygen-induced convulsion significantly (P<0.05, P<0.01). There was no significant difference in the latency between every two groups of rats treated with different doses of indomethacin. But when the rats were administered acetazolamide of 7.5 mg/kg body weight after being pretreated with indomethacin of 20 mg/kg body weight, the outbreak of convulsion was put off remarkably (P<0.05). (2) In comparison with the control, the content of MDA in the group treated with acetazolamide increased significantly (P<0.01), but when the rats were treated with both acetazolamide and indomethacin, the content of MDA was reduced significantly both in 6 and 16 min exposure time projects (P<0.05, P<0.01). These results suggest that acetazolamide which dilates the brain arterioles can obviously shorten the latency of hyperbaric oxygen-induced convulsion and aggravate the oxidation of the brain. Indomethacin can resist acetazolamideos effect on the latency and oxidation level when the animals were exposed to the hyperbaric oxygen. The activity of carbonic anhydrase correlates closely with the oxidation injury.

Effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion / 生理学报

The purpose of the present study was to explore the relation between the modulation of cerebral blood flow and the latency of hyperbaric oxygen-induced convulsion. There were two parts in this study. First, the effect of acetazolamide on the latency of hyperbaric oxygen-induced convulsion was observed. 32 Sprague-Dawley (SD) rats were randomly divided into four groups: the acetazolamide 200, 20, 2 mg/kg body weight and normal saline (NS) group. The animals were given intraperitoneally acetazolamide or NS, respectively, before being exposed to the pressure of 6 ATA (absolute atmosphere) of pure oxygen. The time from exposure to the onset of seizure (clonic-tonic convulsion) was recorded for each animal according to behavioral observation. Second, the changes in maleic dialdehyde (MDA) and the activity of glutathione peroxidase (GSH-PX) were measured after acetazolamide treatment. 40 SD rats were randomly divided into five groups: NS group, 6 min with NS group, 6 min with acetazolamide group, 16 min with NS group, and 16 min with acetazolamide group. The dose of acetazolamide was 20 mg/kg body weight. After injection of NS or acetazolamide, the animals were subjected to the pressure of 6 ATA of pure oxygen in respect to its time course group. The rats were decapitated and the cortex, hippocampus, and striatum of brains were dissected and homogenized. The content of MDA and the activity of GSH-PX in these tissues were determined. We found that (1) there was a significant difference in the latency of hyperbaric oxygen-induced convulsion between the acetazolamide 200 mg/kg group and the NS control group, as well as between the acetazolamide 20 mg/kg group and the NS control group (P<0.01), whereas there was no significant difference between the NS group and the acetazolamide 2 mg/kg weight group (P>0.05). The latency of these groups were listed as follows: 9.78+/-1.94 min for 200 mg/kg body weight group, 10.92+/-1.68 min for 20 mg/kg body weight group, 24.32+/-4.33 min for 2 mg/kg body weight group and 22.02+/-4.32 min for NS control group. (2) there was no significant difference between all groups in the activity of GSH-PX, though it varied with the oxidation levels. In the cortex and hippocampus, the activity of GSH-PX boosted up at first, but with the progress of the oxidation it was impaired. In the striatum, the activity of GSH-PX increased stepwise with the aggravation of the oxidation. The MDA content in the cortex increased significantly in the group of 6 min with acetazolamide (P<0.01), as well as the group of 16 min with acetazolamide group both in cortex and hippocampus (P<0.01, P<0.05). The MDA content of all groups is correlated with the dose of acetazolamide and the exposure time. These results suggest that acetazolamide which dilates the brain arteriolar obviously shortens the latency of hyperbaric oxygen-induced convulsion, and that acetazolamide dilates the vessels and increases the supply of the oxygen breaking into the brain tissues and aggravates the oxidation. The hyperbaric oxygen-induced convulsion correlates closely with the oxidation injury.