Maternal immunoglobulins are distributed in the offspring's brain to support the maintenance of cortical interneurons in the postnatal period.

It is known that maternal immunoglobulins (Igs) are transferred to the offspring across the placenta. However, receiving maternal Igs, especially before the blood-brain barrier (BBB) is formed in the offspring's brain, carries the risk of transferring some brain-reactive Igs. It is thus hypothesized that there may be some unknown benefit to the offspring's brain that overweighs this risk. In this study, we show that the Ig detected in the embryonic/perinatal mouse brain is IgG not produced by the pups themselves, but is basically transferred from the mother across the placenta using the neonatal Fc receptor (FcRn) during embryonic stages. The amount of IgG in the brain gradually decreases after birth, and almost disappears within 3 weeks postnatally. IgG is detected on axon bundles, microglia, and some meningeal cells, including border-associated macrophages (BAMs), endothelial cells, and fibroblasts. Using Fcer1g knock-out (KO) mice, we show that BAMs and microglia receive maternal IgG in an Fc receptor γ chain (FcRγ)-dependent manner, but IgG on other meningeal cells and axon bundles is received independently of the FcRγ. These results suggest that maternal IgG may be used in multiple ways by different mechanisms. In maternal IgG-deficient mice, the number of interneurons in the cerebral cortex is not altered around birth but is reduced postnatally, suggesting that receipt of maternal IgG is necessary for the maintenance of cortical interneurons in the postnatal period. These data suggest that maternal IgG has an important function in the developing brain, where neither obvious inflammation nor infection is observed.

Interactions between neural cells and blood vessels in central nervous system development.

The sophisticated function of the central nervous system (CNS) is largely supported by proper interactions between neural cells and blood vessels. Accumulating evidence has demonstrated that neurons and glial cells support the formation of blood vessels, which in turn, act as migratory scaffolds for these cell types. Neural progenitors are also involved in the regulation of blood vessel formation. This mutual interaction between neural cells and blood vessels is elegantly controlled by several chemokines, growth factors, extracellular matrix, and adhesion molecules such as integrins. Recent research has revealed that newly migrating cell types along blood vessels repel other preexisting migrating cell types, causing them to detach from the blood vessels. In this review, we discuss vascular formation and cell migration, particularly during development. Moreover, we discuss how the crosstalk between blood vessels and neurons and glial cells could be related to neurodevelopmental disorders.

Volatile organic compounds from human skin as biomarkers of menstruation phase and severity of premenstrual syndrome: An exploratory pilot study.

Background and aim: Numerous women of reproductive age experience physical or mental discomfort during their natural menstrual cycle due to paramenstrual symptoms, such as premenstrual syndrome (PMS). To date, there is no established biomarker for the diagnosis of PMS. This study investigated the relationship between skin gas composition and menstruation cycles, and evaluated the possibility of skin gas composition as a biomarker of paramenstrual symptoms. Methods: We conducted an exploratory pilot study. Healthy Japanese women (aged 20-29 years) underwent blood and skin gas analyses on 1 day corresponding to menstruation, preovulatory, middle luteal, and late luteal phases. Skin gas was collected from the cubital fossa and armpit using a Passive Flux Sampler; samples were analyzed for 65 volatile organic compounds (VOCs) by gas chromatography-mass spectrometry (GC-MS). Non-parametric statistical analysis was performed to identify VOCs related to the menstrual cycle, levels of female hormones, and severity of PMS. Results: Fourteen women participated; of those, 12 completed the study. Regarding the relationship with the menstrual cycles, seven and four VOCs were significantly and marginally changed, respectively, at the cubital fossa during menstruation. Of those 11 compounds, 10 were also correlated with the levels of serum female hormones. At the armpit, five and three compounds were significantly and marginally changed, respectively, during menstruation. Of those eight compounds, five were also correlated with the levels of serum female hormones. In the study of PMS severity, analysis of the changes in VOCs suggested that ketones and fatty acids are increased during menstruation in the severe PMS group versus the mild PMS group. Conclusions: The results of this study suggest that certain VOCs emitted in skin gas related to the menstrual cycle, levels of female hormones, and severity of PMS. These findings may advance the metabolic understanding and development of diagnostic biomarkers for menstruation-related symptoms.

Effect of fluid replacement with green tea on body fluid balance and renal responses under mild thermal hypohydration: a randomized crossover study.

PURPOSE: Maintaining an appropriate hydration level by ingesting fluid in a hot environment is a measure to prevent heat-related illness. Caffeine-containing beverages, including green tea (GT), have been avoided as inappropriate rehydration beverages to prevent heat-related illness because caffeine has been assumed to exert diuretic/natriuretic action. However, the influence of caffeine intake on urine output in dehydrated individuals is not well documented. The aim of the present study was to examine the effect of fluid replacement with GT on body fluid balance and renal water and electrolyte handling in mildly dehydrated individuals. METHODS: Subjects were dehydrated by performing three bouts of stepping exercise for 20 min separated by 10 min of rest. They were asked to ingest an amount of water (H2O), GT, or caffeinated H2O (20 mg/100 ml; Caf-H2O) that was equal to the volume of fluid loss during the dehydration protocol; fluid balance was measured for 2 h after fluid ingestion. RESULTS: The dehydration protocol induced hypohydration by ~ 10 g/kg body weight (~ 1% of body weight). Fluid balance 2 h after fluid ingestion was significantly less negative in all trials, and the fluid retention ratio was 52.2 ± 4.2% with H2O, 51.0 ± 5.0% with GT, and 47.9 ± 6.2% with Caf-H2O; those values did not differ among the trials. After rehydration, urine output, urine osmolality, and urinary excretions of osmotically active substances, sodium, potassium and chloride were not different among the trials. CONCLUSION: The data indicate that ingestion of GT or an equivalent caffeine amount does not worsen the hydration level 2 h after ingestion and can be effective in reducing the negative fluid balance for acute recovery from mild hypohydration. TRIAL REGISTRATION: ISRCTN53057185; retrospectively registered.

Estradiol replacement improves high-fat diet-induced insulin resistance in ovariectomized rats.

The role of 17ß-estradiol (E2) in high-fat diet (HFD)-induced alteration of the protein kinase B (Akt) signaling pathway in ovariectomized (OVX) rats is unclear. Therefore, we examined whether chronic estrogen replacement restores HFD-induced impairment in insulin sensitivity by its effects concomitant with alterations in the Akt isoform 2 (Akt2) and Akt substrate of 160 kDa (AS160) phosphorylation in muscles of OVX rats. Nine-week-old female Wistar rats underwent ovariectomy under anesthesia; after 4 weeks, subcutaneous implantation of either E2 or placebo (PL) pellets was performed, and HFD feeding was initiated. Intravenous glucose tolerance tests were performed to assess insulin sensitivity. Following insulin injection into rats' portal vein, the liver and gastrocnemius muscle were dissected for insulin signaling analysis. We observed that HFD increased energy intake and body weight in the PL group; however, it was temporarily decreased in the E2 group. Adipose tissue accumulation was larger in HFD-fed rats than in normal chow diet (NCD)-fed rats in the PL group; however, this difference was not observed in the E2 group. HFD reduced insulin sensitivity in the PL group only. In vivo insulin stimulation increased Akt2 phosphorylation in the muscles of NCD-fed rats in both groups. In contrast, HFD affected insulin-stimulated phosphorylation of Akt2 and AS160 in the muscles of rats in the PL group but not in the E2 group. Our data suggest that E2 replacement improves HFD-induced insulin resistance, and this effect is accompanied by the alterations in the Akt2 and AS160 phosphorylation in insulin-stimulated muscles of OVX rats.

Endogenous Androgens Diminish Food Intake and Activation of Orexin A Neurons in Response to Reduced Glucose Availability in Male Rats.

Sex steroids modify feeding behavior and body weight regulation, and androgen reportedly augments food intake and body weight gain. To elucidate the role of endogenous androgens in the feeding regulation induced by reduced glucose availability, we examined the effect of gonadectomy (orchiectomy) on food intake and orexin A neuron's activity in the lateral hypothalamic/perifornical area (LH/PFA) in response to reduced glucose availability (glucoprivation) induced by 2-deoxy-d-glucose (2DG) administration in male rats. Rats (7W) were bilaterally orchiectomized (ORX group) or sham operated (Sham group). Seventeen days after the surgery, food intake response to 2DG (400 mg/kg, i.v.) was measured for 4 h after the infusion. The same experiment was performed for the immunohistochemical examination of c-Fos-expressing orexin A neurons in the LH/PFA and c-Fos expression in the arcuate nucleus (Arc). Food intake induced by glucoprivation was greater in the ORX group than the Sham group, and the glucoprivation-induced food intake was inversely correlated with plasma testosterone concentration. Glucoprivation stimulated c-Fos expression of the orexin A neurons at the LH/PFA and c-Fos expression in the dorsomedial Arc. The number and percentage of c-Fos-expressing orexin A neurons in the LH/PFA and c-Fos expression in the dorsomedial Arc were significantly higher in the ORX group than the Sham group. This indicates that endogenous androgen, possibly testosterone, diminishes the food intake induced by reduced glucose availability, possibly via the attenuated activity of orexin A neuron in the LH/PFA and neurons in the dorsomedial Arc.

Estradiol Replacement Improves High-Fat Diet-Induced Obesity by Suppressing the Action of Ghrelin in Ovariectomized Rats.

This study aims to investigate the effects of estradiol replacement on the orexigenic action of ghrelin in ovariectomized (OVX) obese rats fed with a high-fat diet (HFD). Four weeks after OVX at 9 weeks of age, Wistar rats were subcutaneously implanted with either 17ß-estradiol (E2) or placebo (Pla) pellets and started on HFD feeding. After 4 weeks, growth hormone-releasing peptide (GHRP)-6, a growth hormone secretagogue receptor (GHSR) agonist injected intraperitoneally, induced changes in HFD intake, and c-Fos-positive neurons in the hypothalamic arcuate nucleus (ARC) were measured in both groups. The ghrelin protein and mRNA levels, as well as GHSR protein in stomach, were analyzed by Western blotting and real-time PCR. HFD increased energy intake and body weight in the Pla group, while it temporarily reduced these in the E2 group. GHRP-6 enhanced HFD intake and activated neurons in the ARC only in the Pla group. Furthermore, gastric ghrelin and GHSR protein levels were lower in the E2 group than in the Pla group, but plasma acyl ghrelin levels were similar in both groups. Our results suggest that E2 replacement improves obesity by inhibiting the orexigenic action of ghrelin via downregulation of ghrelin and its receptor in stomach in HFD-fed OVX rats.

Fluoxetine Mimics the Anorectic Action of Estrogen and Its Regulation of Circadian Feeding in Ovariectomized Female Rats.

Our previous study demonstrated that chronic estrogen replacement in ovariectomized rats reduces food intake and augments c-Fos expression in the suprachiasmatic nucleus (SCN), specifically during the light phase. Here, we hypothesized that serotonergic neurons in the central nervous system (CNS), which have anorectic action and play a role in regulating circadian rhythm, mediate the light phase-specific anorectic action of estrogen, and that selective serotonin reuptake inhibitors (SSRIs) mimic the hypophagic action of estrogen. Female Wistar rats were ovariectomized and treated with estradiol (E2) or cholesterol by subcutaneously implanting a silicon capsule containing E2 or cholesterol. Then, half of the cholesterol-treated rats were injected with the SSRI fluoxetine (5 mg/kg) (FLX group), while the remaining rats in the cholesterol-treated group (CON group) and all those in the E2 group were injected with saline subcutaneously twice daily at the onsets of the light and dark phases. Both E2 and FLX reduced food intake during the light phase but not the dark phase, and reduced body weight gain. In addition, both E2 and FLX augmented the c-Fos expression in the SCN, specifically during the light phase. These data indicate that FLX exerts estrogen-like antiobesity and hypophagic actions by modifying circadian feeding patterns, and suggest that estrogen regulates circadian feeding rhythm via serotonergic neurons in the CNS.

Endurance running exercise is an effective alternative to estradiol replacement for restoring hyperglycemia through TBC1D1/GLUT4 pathway in skeletal muscle of ovariectomized rats.

Menopause is a risk factor for impaired glucose metabolism. Alternative treatment of estrogen for postmenopausal women is required. The present study was designed to investigate the effects of 5-week endurance running exercise (Ex) by treadmill on hyperglycemia and signal pathway components mediating glucose transport in ovariectomized (OVX) placebo-treated rats, compared with 4-week 17ß-estradiol (E2) replacement or pair-feeding (PF) to the E2 group. Ex improved the hyperglycemia and insulin resistance index in OVX rats as much as E2 or PF did. However, Ex had no effect on body weight gain in the OVX rats. Moreover, Ex enhanced the levels of GLUT4 and phospho-TBC1D1 proteins in the gastrocnemius of the OVX rats, but E2 or PF did not. Instead, the E2 increased the Akt2/AS160 expression and activation in the OVX rats. This study suggests that endurance Ex training restored hyperglycemia through the TBC1D1/GLUT4 pathway in muscle by an alternative mechanism to E2 replacement.

Effect of the menstrual cycle phase on foot skin temperature during menthol application in young women.

According to the literature, the arteriovenous anastomoses in the peripheral parts (ex. hands and feet) respond thermal stimulation susceptibly. Thus, the feet are sensitive to cold stimulation. The aim of the present study was to investigate the effect of menstrual cycle on skin temperature (Tsk) of the foot during menthol application in young women. Tsk and partial cutaneous blood flow in the foot, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness during the preovulatory (P), luteal (L), and menstrual (M) phases during menthol application in young women using thermography, laser Doppler flowmetry, a digital blood pressure monitor, and VAS scale were examined at 25 °C. After application of the 0.5% menthol solution to the right foot, the measurements were continued for 20 min. The Tsk of the second and third right toes in the P phase were lower than that in the L phase. The Tsk of the little right toe in the P phase was lower than that in the L and M phases. No significant differences were observed in the Tsk of the dorsum of right foot, cutaneous Laser-Doppler flow in the right great toe, tympanic temperature, blood pressure, heart rate, thermal sensation and pleasantness among the phases. The menstrual cycle phase did not affect Tsk in the dorsum of the foot, but it affected Tsk in some toes during menthol application.

Role of the Immune System in the Development of the Central Nervous System.

The central nervous system (CNS) and the immune system are both intricate and highly organized systems that regulate the entire body, with both sharing certain common features in developmental mechanisms and operational modes. It is known that innate immunity-related molecules, such as cytokines, toll-like receptors, the complement family, and acquired immunity-related molecules, such as the major histocompatibility complex and antibody receptors, are also expressed in the brain and play important roles in brain development. Moreover, although the brain has previously been regarded as an immune-privileged site, it is known to contain lymphatic vessels. Not only microglia but also lymphocytes regulate cognition and play a vital role in the formation of neuronal circuits. This review provides an overview of the function of immune cells and immune molecules in the CNS, with particular emphasis on their effect on neural developmental processes.

Correlations between "hie-sho" interview score and progesterone, fat intake, and Kupperman index in pre- and post-menopausal women: a pilot study.

Japanese menopausal women who feel cold, even in a warm room, are said to be experiencing "hie-sho." We assessed the magnitude of coldness by a "hie-sho" interview score. The association between the magnitude of coldness and female hormones, fat intake, and menopausal symptoms is unknown. The aim of the present study was to elucidate the relationship between the hie-sho interview scores and female hormones, fat intake, Kupperman index in pre- (pre group) and post- (post group) menopausal women. The hie-sho interview scores, Kupperman index questionnaire results, dietary survey to analyze fat intake, and body weight were analyzed, and plasma estradiol, progesterone, and lipid levels were measured in the subjects in the pre (n = 9) and post (n = 11) groups. Plasma female hormones and fat intake were different, but the total Kupperman index was not different between pre and post groups. Plasma progesterone was positively correlated with the hie-sho score only in the post group. Plasma triglyceride was positively correlated with the hie-sho score only in the pre group. Intake of cholesterol, arachidonic acid, and docosapentaenoic acid was negatively correlated with the hie-sho score only in the pre group. The positive correlation between total Kupperman index and hie-sho score was observed only in the pre group. These results indicated that progesterone level was related to coldness in post-menopausal women. Fat intake, plasma triglyceride, and menopausal symptoms may be related to coldness in pre-menopausal women.

The effect of menstrual cycle phase on foot skin temperature during mild local cooling in young women.

Japanese women can experience a sensation of cold feet in daily life. It is possible that this sensation of coldness in feet may be associated with female hormones, but to date the effect of menstrual cycle phase on the skin temperature (Tsk) of the foot during local cooling is unknown. We therefore examined Tsk and partial cutaneous blood flow in the foot during the follicular (F) and luteal (L) phases of the menstrual cycle in women experiencing local cooling. Tsk was measured in the toes and the dorsum of the left foot using infrared thermography, while cutaneous blood flow was evaluated in the big toe of the left foot using laser Doppler flowmetry (LDF), both at 28 °C. Mild local cooling (24.7 °C) was then applied for 30 min to the right foot. During cooling of the right foot, no significant differences in Tsk were observed between the F and L phases in either the toes of the left foot or the dorsum of the left foot of all subjects. However, cutaneous blood flow determined by LDF in the big toe of the left foot was greater in the F phase than in the L phase. These results suggest that the menstrual cycle phase did not affect Tsk in the foot, but it did affect cutaneous blood flow in the big toe during mild local cooling.

Respiratory rate is an inadequate parameter of ventilation in non-intubated sedation.

We compared the respiratory rate (RR) and transcutaneous carbon dioxide pressure ([Formula: see text]) during intravenous sedation (IVS), to determine whether RR is a useful parameter for monitoring ventilation. This was a prospective cohort study. The study sample comprised dental patients who received IVS via propofol or midazolam administration at Nippon Dental University Hospital. We simultaneously measured RR (through capnography), [Formula: see text] (using the [Formula: see text] monitor), and percutaneous oxygen saturation (SpO2). RR was the predictor and the outcome variable was [Formula: see text]. Data were analyzed by Dunnett's test and Pearson's correlation coefficient. P < 0.05 was considered statistically significant. The study sample consisted of 15 patients. No significant changes were identified in the RR and SpO2 measurements over time. However, [Formula: see text] values obtained from 20 to 40 min after induction of sedation were significantly higher than baseline values (P < 0.05). A correlation was found between RR and [Formula: see text] (P < 0.05), but the correlation coefficient was low (r = 0.22), indicating a weak correlation between these two factors. The results of this study suggest that RR is an inadequate parameter for monitoring ventilation during IVS; however, [Formula: see text] may be useful for monitoring.

Estrogen replacement enhances insulin-induced AS160 activation and improves insulin sensitivity in ovariectomized rats.

Menopause predisposes women to impaired glucose metabolism, but the role of estrogen remains unclear. In this study, we examined the effects of chronic estrogen replacement on whole body insulin sensitivity and insulin signaling in ovariectomized rats. Female Wistar rats aged 9 wk were ovariectomized under anesthesia. After 4 wk, pellets containing either 17ß-estradiol (E2) or placebo (Pla) were subcutaneously implanted in the rats. After 4 wk of treatment, the intra-abdominal fat accumulation was greater in the Pla group than that in the E2 group. Hyperinsulinemic-euglycemic clamp analysis and intravenous glucose tolerance test revealed that insulin sensitivity was significantly lower in the Pla group than in the E2 group. In addition, Western blotting showed that in vivo insulin stimulation increased protein kinase B (Akt) phosphorylation to a similar degree in the gastrocnemius and liver of both groups, but phosphorylated Akt2 Ser474 was enhanced in the muscle of the E2 group compared with the Pla group. Moreover, insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) Thr642 was observed only in the E2 group, resulting in the difference between the two groups. Additionally, AS160 protein and mRNA levels were higher in muscle of the E2 group than the Pla group. In contrast, E2 replacement had no effect on glucose transporter 4 protein levels in muscle and glycogen synthase kinase-3ß in muscle and liver. These results suggest that estrogen replacement improves insulin sensitivity by activating the Akt2/AS160 pathway in the insulin-stimulated muscle of ovariectomized rats.

Foot pressure analysis of gait pattern in older Japanese females requiring different personal care support levels.

[Purpose] This study evaluated gait parameters and foot pressure in two regions of the feet among older females with different personal care support needs to analyze factors that contribute to higher support requirements. [Subjects and Methods] Thirty-two older females were divided into support-need and care-need level groups. Gait parameters (speed, cadence, step length, step width, gait angle, toe angle, double support phase, swing phase, and stance phase) and foot pressure during a 5-m walk were measured and analyzed in the two groups. [Results] The percentage of the double support phase on both feet and the right stance phase were significantly higher in the care-need level group, while that of the right swing phase was significantly lower than that of the support-need level group. Additionally, the phase showing peak pressure on the left rear foot was significantly delayed and the left forefoot pressure in the terminal stance was significantly lower in the care-need level group than in the support-need level group. [Conclusion] These findings show that the temporal duration parameters and foot pressure on a particular side were significantly different between the two groups and suggest that these differences were associated with a higher care level.

Are Wireless Electronic Stethoscopes Useful for Respiratory Rate Monitoring During Intravenous Sedation?

PURPOSE: Wireless stethoscopes can measure respiratory rate noninvasively and continuously, but there are no reports of their use during dental treatment. This study evaluated the usefulness of wireless stethoscopes during dental procedures requiring intravenous sedation (IVS). MATERIALS AND METHODS: This study was a prospective cohort study. The study sample consisted of dental patients who received IVS by propofol or midazolam administration at the Nippon Dental University Hospital (Tokyo, Japan). The predictor was respiratory rate measured using the wireless stethoscope (BrRR), and the outcome variable was respiratory rate measured during capnography (RR). Pearson correlation coefficients and paired-samples t tests were used for data analysis. A P value less than .05 was considered statistically significant. RESULTS: The study sample consisted of 12 patients. BrRR and RR were significantly and positively correlated (r = 0.93, P < .01). The mean ± standard deviation of BrRR was 14.16 ± 2.67 and that of RR was 14.32 ± 2.77. There was no significant difference between the 2 groups (P = .27). CONCLUSIONS: The results of this study suggest that wireless stethoscopes are suitable for monitoring respiratory rate during dental procedures requiring IVS because their use is as accurate as capnography.

Estrogen replacement attenuates stress-induced pressor responses through vasorelaxation via ß2-adrenoceptors in peripheral arteries of ovariectomized rats.

We examined whether chronic estrogen replacement has an inhibitory effect on stress-induced pressor responses via activation of ß2-adrenoceptor (AR) in peripheral arteries of ovariectomized rats. Female Wistar rats aged 9 wk were ovariectomized. After 4 wk, pellets containing either 17ß-estradiol (E2) or placebo (Pla) were subcutaneously implanted into the rats. After 4 wk of treatment, rats underwent cage-switch stress, and, in a separate experiment, a subset received an infusion of isoproterenol (ISO) with or without pretreatment with the ß1-AR blocker atenolol or the ß2-AR blocker butoxamine. In addition, the isolated mesenteric artery was used to assess the concentration-related relaxing responses to ISO and the ß1- or ß2-AR mRNA level. The cage-switch stress-induced pressor response was significantly attenuated in the E2-treated group compared with the Pla-treated group. Pretreatment with atenolol reduced blood pressure responses in both groups. However, butoxamine enhanced the pressor response only in the E2-treated group, resulting in no difference between the two groups. In addition, the intravenous ISO-induced depressor response was significantly enhanced in the E2-treated group compared with the Pla-treated group. Furthermore, the difference in the depressor response was abolished by pretreatment with butoxamine but not by atenolol. In the isolated mesenteric artery, butoxamine caused a rightward shift in ISO-induced concentration-related relaxation in the E2-treated group. The ß2-AR mRNA level in the mesenteric artery was higher in the E2-treated group than in the Pla-treated group. These results suggest that estrogen replacement attenuated the stress-induced pressor response probably by suppressing vasoconstriction via activation of ß2-ARs in peripheral arteries of ovariectomized rats. NEW & NOTEWORTHY In this study, we show, for the first time, that estrogen replacement has an inhibitory effect on the psychological stress-induced pressor response through vasorelaxation via ß2-adrenoceptors, probably due to overexpression of ß2-adrenoceptor mRNA, in peripheral arteries of ovariectomized rats.