Abstract Neonatal maternal separation (MS), stressful experience early in life, leads to the development of depression-like behaviors in the offspring later in life. This study was conducted to ...define the neural basis of depression-like behaviors observed in our MS model. Sprague–Dawley pups were separated from dam for 3 h daily during the first 2 weeks of birth (MS) or left undisturbed (NH). All pups were sacrificed on postnatal day 41 with/without 1 h of restraint stress. Restraint stress significantly increased c-Fos expression in the nucleus accumbens (NAcb) of NH pups, but not in MS. In NH pups, restraint stress increased dopamine levels not only in the NAcb but also in the midbrain dopamine neurons; however, these increases were not observed in MS. Gene expression of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) was increased by acute restraint in NH pups, but not in MS pups. The raphe serotonin level was lower in MS than in NH, and not significantly changed by acute restraint neither in NH nor in MS. Results reveal that experience of neonatal MS may lead to a long-term suppression in the mesolimbic dopamine system of the offspring later in life, in which an epigenetic control may be implicated, such as suppressed gene expression of TH in the midbrain. We conclude that a decreased activity of the mesolimbic dopamine system may play a role in the pathophysiology of depression-like behaviors by neonatal MS, in addition to a decreased serotonin level in the raphe nucleus.
The mobile network operators should expand their network capacity as service traffic increases in mobile networks. It is important to balance network capacity and traffic volume in terms of service ...quality and operating costs, and this network balance can be quantified by the capacity margin, which is defined as the difference between network capacity and traffic volume. There are two approaches to assess the network capacity: single-cell and national scale. However, the single-cell approach has too narrow to estimate the whole operator network, and the national scale approach should consider regional traffic density distribution. This Letter proposes a methodology for assessing the capacity margin from the perspective of traffic-intensive regions where the actual network balance is determined. The authors introduce the concept of a virtual sample region that consists of traffic-intensive cells in the metropolitan area. Then they show the methodology to estimate and predict the network capacity and traffic trends in this region. Finally, they derive the capacity margin of the mobile network. They used the real measured data in the top 10% traffic-intensive cells about three years in Seoul, South Korea, and evaluated 4G downlink capacity margin in this region until 2024.
Background Gases produced by intestinal flora may modulate intestinal motor function in healthy individuals as well as those with functional bowel disease. Methane, produced by enteric bacteria in ...the human gut, is associated with slowed intestinal transit and constipation. The effects of hydrogen, another main gas produced by bacterial fermentation in the gut, on small bowel and colonic motor function remains unrecognized. Therefore, we set out to investigate whether intestinal gases including methane and hydrogen could influence the small bowel motility and colonic transit.
Methods Guinea pig ileum was placed in the peristaltic bath with tension transducers attached to measure velocity and amplitude of peristaltic contraction before and after the infusion of control, hydrogen, and methane gases. Also, changes in the intraluminal pressures were monitored before and after the gas infusions.
Key Results Methane decreased peristaltic velocity and increased contraction amplitude significantly of guinea pig ileum (P < 0.05). The AUC of intraluminal pressure was significantly increased with methane in guinea pig ileum (P < 0.05). In a second experiment, guinea pig colon was placed in the peristaltic bath to measure transit time before and after control, hydrogen, methane, and methane‐hydrogen mixture gas infusions. Hydrogen shortened colonic transit time by 47% in the proximal colon, and by 10% in the distal colon, when compared with baselines (P < 0.05).
Conclusions & Inferences Methane delayed ileal peristaltic conduction velocity by augmenting contractility. Hydrogen shortened colonic transit, and that effect was more prominent in the proximal colon than distal colon.
Food deprivation (FD) increases hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels and decreases proopiomelanocortin (POMC) mRNA levels; refeeding restores these levels. ...We determined the time course of changes in hypothalamic NPY, AGRP, and POMC mRNA levels on refeeding after 24 h FD in C57BL mice by in situ hybridization. After 24 h deprivation, mice were refed with either chow or a palatable mash containing no calories or were injected with murine leptin (100 microg) without food. Mice were perfused 2 or 6 h after treatment. Food deprivation increased hypothalamic NPY mRNA (108 +/- 6%) and AGRP mRNA (78 +/- 7%) and decreased hypothalamic POMC mRNA (-15 +/- 1%). Refeeding for 6 h, but not 2 h, was sufficient to reduce (but not restore) NPY mRNA, did not affect AGRP mRNA, and restored POMC mRNA levels to ad libitum control levels. Intake of the noncaloric mash had no effect on mRNA levels, and leptin administration after deprivation (at a dose sufficient to reduce refeeding in FD mice) was not sufficient to affect mRNA levels. These results suggest that gradual postabsorptive events subsequent to refeeding are required for the restoration of peptide mRNA to baseline levels after food deprivation in mice.
Objective: To examine the neurobiological basis of bingeing-related eating disorders using an animal model system. Design: Sprague-Dawley pups were separated from dam for 3 h daily during the first ...two weeks of birth (maternal separation (MS)), or left undisturbed (non-handled (NH)). Pups were subjected to repeated fasting/refeeding (RF) cycles; that is, 24 h food deprivation and 24 h RF (NH/RF or MS/RF), or had free access to food and water (NH/fed control (FC) or MS/FC) from postnatal day (PND) 28-40. Measurements: Body weight gain and food intake were recorded. The arcuate expression of neuropeptide Y (NPY) and plasma corticosterone levels were analyzed on PND 29 and 40. Results: Decrease in weight gain by repeated fasting/RF cycles was smaller in MS pups than in NH. Interestingly, weight changes responding to fasting or RF increased in MS/RF compared with NH/RF. Compensatory hyperphagia was diminished in NH/RF after the third fasting trial, but persisted in MS/RF throughout the experimental period. The arcuate expression of NPY mRNA responding to food deprivation was blunted, but elevation of plasma corticosterone exaggerated, in the MS group, compared to the NH group, on PND 29 after the first fasting session. However, both the arcuate NPY mRNA and plasma corticosterone levels were increased in MS/RF, but not in NH/RF, on PND 40 after the six sets of fasting/RF cycles, compared to the free FC groups. Conclusion: Experience of neonatal MS may lead to an exaggerated feeding response to repeated fasting/RF challenges at adolescence, perhaps, due to increased responsiveness of the hypothalamic-pituitary-adrenal gland axis. Additionally, the results suggested that an increased action of the hypothalamic NPY may not be necessary to induce compensatory hyperphagia following food deprivation.
Abstract This study was conducted to examine the effect of neonatal maternal separation on the hypothalamic feeding peptides expression in young female offspring. Sprague–Dawley pups were separated ...from dam for 3 h daily during PND 1–14 (MS), or left undisturbed except routine cage cleaning (NH). Weanling female pups were housed in group and the arcuate mRNA levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), and cocaine–amphetamine regulated transcript (CART) were examined at two months of age with or without food deprivation. The basal arcuate expression levels of these peptides did not differ between NH and MS group. However, a 48 h of food deprivation significantly increased NPY mRNA level, and decreased POMC and CART, in the arcuate nucleus of MS females, but not in NH females. Fasting-induced elevation of the plasma corticosterone tended to be greater in MS group than in NH, but the basal levels did not differ between the groups. Plasma leptin levels were decreased in MS females compared with NH, and food deprivation significantly suppressed the leptin levels both in NH and MS groups. Results suggest that MS experience may increase stress vulnerability in female rats and exaggerate the feeding peptides expression in the arcuate nucleus responding to metabolic stress food deprivation.
The aim of this study was to investigate whether neonatal maternal separation (MS) – chronic stress experience in early life – affects the anorectic efficacy of leptin in the offspring at ...adolescence. Sprague–Dawley pups were separated from the dam daily for 3 h during postnatal day 1–14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.
This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02% capsaicin ...into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.
This study was conducted to examine the effects of neonatal maternal separation on the hypothalamic expression of feeding peptides in later life. Pups in maternal separation (MS) groups were ...separated from their dam for 3
h daily from postnatal day (PND) 1–14, while pups in non-handled (NH) groups were left undisturbed. Rats were sacrificed on PND 60 to examine the gene expression of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) in the hypothalamic arcuate nucleus by mRNA in situ hybridization. Half of the rats from each group were food-deprived for 48
h before sacrifice. POMC mRNA expression increased in the free fed MS group compared with the free fed NH group. Food deprivation significantly decreased the arcuate POMC mRNA level in both groups. Body weight gain, basal levels of plasma corticosterone, leptin, and arcuate NPY mRNA were not modulated by experience of neonatal maternal separation. However, fasting-induced increases of plasma corticosterone and arcuate NPY expression were blunted in MS rats. These results suggest that neonatal maternal separation may increase the basal expression level of arcuate POMC mRNA, while inhibit the fasting-induced expression of arcuate NPY mRNA, later in life. Lastly, the altered expression of arcuate NPY mRNA, but not of arcuate POMC mRNA, appeared to be related with altered activity of the hypothalamic-pituitary-adrenal gland axis in offspring by neonatal maternal separation.