BackgroundMicroglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS) induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow.Methods and FindingsHere we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1lowCCR2+CXCR4high, as distinct from CX3CR1highCCR2-CXCR4low resident microglia, and express higher levels of interleukin-1β (IL-1β) but lower levels of tumor necrosis factor-α (TNF-α). Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4+ monocytes in peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a β3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN.ConclusionChronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

Hydrogen (H2) acts as a therapeutic antioxidant. However, there are few reports on H2 function in other capacities in diabetes mellitus (DM). Therefore, in this study, we investigated the role of H2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ)-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H2 promoted 2-[14C]-deoxy-d-glucose (2-DG) uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K), protein kinase C (PKC), and AMP-activated protein kinase (AMPK), although it did not stimulate the translocation of Glut2 in Hep G2 cells. H2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p.) and oral (p.o.) administration. However, long-term p.o. administration of H2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

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Abstract. Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB̸c mice. The plasma nesfatin-1 levels̸visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2-and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels̸VF ratio in the 24-month-old mice was significantly lower compared to that in the 2-and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging.

We examined the association between nutrient intake and prefrailty. Data from 815 older people (63% women) who participated in a community-based health check survey (Tarumizu Study) were analyzed. Prefrailty were defi ned using fi ve parameters (exhaustion, slowness, weakness, low physical activity, and weight loss). Participants with one or more components were considered to belong to the prefrailty group. Nutrition intake was estimated from a validated brief-type self-administered diet history questionnaire. Among the participants, 154 men (52%) and 278 women (54%) were found to be in a status of prefrailty. In men, there were no signifi cant associations between nutrient intake and prefrailty. In women, carbohydrate intake was slightly higher in prefrailty group. Vitamins K, B1, B2, folic acid, pantothenic acid, phosphorus, potassium, calcium, magnesium, iron, zinc, and copper intake was signifi cantly lower in the prefrailty group. Among the nutrients, magnesium was identifi ed as a signifi cant covariate of prefrailty using a stepwise regression method. In women adjusted ORs (95%CI, p value) for prefrailty in the fi rst, second, third, and fourth quartiles of magnesium intake were 1.00 (reference), 0.52 (0.29-0.92, 0.024), 0.51 (0.28-0.95, 0.033), and 0.38 (0.19-0.74, 0.005), respectively, by multivariate logistic regression analysis (variates: age, body mass index, energy intake, supplement use, osteoporosis, magnesium, and protein intake). Protein intake did not related to prefrailty. Protein intake might be suffi cient to prevent prefrailty in the present study. We propose magnesium to be an important micronutrient that prevents prefrailty in community-dwelling older Japanese women.