Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.     

高糖对体外培养Schwann细胞生长及细胞外信号调节激酶1／2磷酸化的影响

目的:探讨高糖对体外培养Schwann细胞生长及细胞外信号调节激酶(ERK)磷酸化的影响.方法:按照培养液中葡萄糖浓度的小同,分为对照组与高糖组.用MTT法检测Schwann细胞生长情况;用ELISA法检测对照组与高糖组ERK1/2磷酸化的程度,以及加入神经源性一氧化氮合成酶(nNOS)抑制剂后ERK1/2磷酸化的程度.结果:高糖浓度下,细胞虽有增殖但幅度及时程明显低于对照组,高糖抑制Schwann细胞生长;随着精浓度的升高.ERK1/2磷酸化的程度逐渐增加,并与加入nNOS抑制剂有相似的表现.结论:高糖抑制Schwann细胞生长,并且降低nNOS的量,减弱一氧化氮(NO)对ERK1/2的抑制作用,导致ERK1/2磷酸化水平升高.     

The role of different subsets of T regulatory cells in controlling autoimmunity

T regulatory cells-in addition to clonal deletion and anergy-are essential for the downregulation of T cell responses to both foreign and self antigens, and for the prevention of autoimmunity. Recent progress has been made in characterising the different subsets of T regulatory cells, the factors that drive their differentiation, and their mode of action. The resolution of these mechanisms will make it possible to use T regulatory cells therapeutically in human autoimmune diseases.     

Diabetes mellitus in Huntington disease

There have been conflicting reports that individuals with Huntington disease (HD) are prone to abnormalities of carbohydrate metabolism. In this study information about the incidence and control of diabetes mellitus in 620 probands (278 living, 332 deceased) with HD and in their first and second degree relatives was obtained by questionnaire method from participants of the National HD Research Roster. Among the probands, 65 individuals (10.5%) were identified by the informant or verified by examination of Roster family records as diabetic. The prevalence of diabetes, particularly among those less than 50 years of age, is significantly greater than corresponding figures among the general U.S. Caucasian population (Scott 1977, Krolewski & Warram 1985). Incidence rates were not calculated because of ascertainment and other biases in the data. Results from the analysis of family data indicate that HD affected relatives of an HD proband with diabetes are 7 times as likely to have diabetes over the proband's non-HD relatives. A non-diabetic HD proband is equally likely to have an HD or non-HD relative with diabetes.     

The reproducibility of the oral glucose tolerance test over long (5 years) and short periods (1 week)

Summary Three oral glucose tolerance tests (oGTT) have been performed in 312 non-diabetic relatives of diabetics over a period of 10 years. In a second study 6 identical oGTT's have been performed at weekly intervals in 55 individuals. In this study the variance, calculated from the logarithmic values, increased in the following order: fasting (0.026), 1 h (0.035), 2 h (0.044) and 3 h values (0.047). The sum of the 1 h and 2 h values showed the lowest variance (0.024). No significant difference of the variances was found in the 43 individuals in whom both the long-term and the short-term studies have been performed. Thus, a great proportion of the total variance of glucose observed over longer periods only represents a random variation. This random variation is much higher than most other factors which might influence the result of an oGTT. A diagnosis based on a single oGTT is of only limited value.Supported by a grant from Deutsche Forschungsgemeinschaft (Ko 457/8)     

The metabolic response to prolonged walking in fed and fasted men

Summary Six healthy men walked 37 km (23 miles) per day over a 3-lap course for each of 4 consecutive days. Subjects were allowed breakfast and an unrestricted diet was consumed after completion of the walk, but no food was consumed during or between laps. At a later date the same subjects walked over the same course after an overnight fast and without breakfast. Completion time for each lap was 139±1 min (mean ±SE) and exercise intensity was equivalent to 17±1% . Mean 24h energy intake was 14.5±0.8 MJ during the fed walk. Estimated daily energy expenditure was 12.0 MJ. Blood glucose concentration fell significantly on the first, third and fourth days of the fed walk, but no subject became hypoglycaemic. Glucose concentration did not fall during the fasted walk and was significantly higher pre-exercise and at the end of laps one and three when compared to the first day of the fed walk. Blood alanine concentration fell significantly after the end of the first lap of each day of the fed walk but not during the fasted walk. Blood lactate levels did not change during the course of either walk. Plasma free fatty acid, glycerol and blood 3-hydroxybutyrate concentrations were unchanged during the passage of the first lap on each day of the fed walk, but all three had increased significantly by the end of the first lap of the fasted walk. The elevations from rest to the end of each day's walking for these three metabolites were of similar magnitude when comparing each day of the fed walk and the fed and fasted walks. The present experiment indicates that feeding a mixed diet can affect the pattern of substrate mobilization in a similar manner to that seen during more strenuous exercise. It also appears that the pattern of fuel substrate mobilization is very similar from one day to the next providing dietary intake is similar.     

Adaptive modification of ingestive behavior in beach mice (Peromyscus polionotus).

The ability of an inland and beach race of the old-field mouse to use increasing concentrations of NaCl solutions was compared. Inland mice drank significantly more fluid at all concentrations than did beach mice. These differences became more pronounced as the salt concentration was increased. Food consumption was similar in both races while drinking water or a dilute salt solution, but beach mice ate significantly greater amounts when the concentration of salt was increased above 0.2 M. Weight losses on salt solutions were approximately equal in both races, although beach mice survived longer and tolerated the higher concentrations better. There was no difference in the ability of the races to concentrate urine or excrete Na⁺. When given a choice of distilled water or two salt solutions, beach mice consumed significantly more water (77%) than salt solutions (23%) whereas inland mice drank approximately equal amounts of water (54%) and salt solutions (46%). When deprived of anything to drink, beach mice almost stopped eating for the first two days while inland mice did not reduce their food consumption as quickly and died sooner. Thus, it appears that adaptive modifications of ingestive behavior are important for survival in habitats where salt accumlates and summer droughts may be a problem.     

Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6–8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.     

Interleukin-15 is not required for the induction or maintenance of orally induced peripheral tolerance

Orally induced tolerance is a physiologically relevant form of peripheral tolerance, which is believed to be important for the prevention of pathological immune responses in the gut. Of several mechanisms proposed to mediate oral tolerance, one that has received much attention recently is the concept of regulatory CD4+ T cells. As recent studies have suggested that interleukin (IL)-15 may be important for the differentiation and maintenance of regulatory CD4+ T cells, we have examined the role of IL-15 in oral tolerance, using a soluble form of the IL-15 receptor (sIL-15R) which blocks the biological effects of IL-15 in vivo. Oral tolerance induced by feeding mice ovalbumin (OVA) in a low-dose regimen believed to induce regulatory T cell activity was not affected by the administration of sIL-15R during either the induction or maintenance phase of tolerance. Thus, oral tolerance does not involve an IL-15-dependent mechanism.