Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1.

Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1.     

On the question of American eels,Anguilla rostrata versus European eels,Anguilla anguilla

Zusammenfassung Der amerikanische AalAnguilla rostrata (2n=38; 20M+18A) gehört einer anderen Spezies an als der europäischeAnguilla anguilla (2n=38; 32M+6A).

---

---

This work was supported in part by a grant No. CA 05138 from the National Cancer Institute, U.S. Public Health Service.     

Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta

Protein kinase C (PKC), which comprises 11 closely related isoforms, has been implicated in a wide variety of cellular processes, such as growth, differentiation, secretion, apoptosis and tumour development. Among the PKC isotypes, PKC-delta is unique in that its overexpression results in inhibition of cell growth. Here we show that mice that lack PKC-delta exhibit expansion of the B-lymphocyte population with the formation of numerous germinal centres in the absence of stimulation. The rate of proliferation in response to stimulation was greater for B cells from PKC-delta-deficient mice than for those from wild-type mice. Adoptive transfer experiments suggested that the hyperproliferation phenotype is B-cell autonomous. Production of interleukin-6 was markedly increased in B cells of PKC-delta-null mice as a result of an increase in the DNA-binding activity of NF-IL6. Furthermore, the PKC-delta-deficient mice contain circulating autoreactive antibodies and display immune-complex-type glomerulonephritis, as well as lymphocyte infiltration in many organs. These results suggest that PKC-delta has an indispensable function in negative regulation of B-cell proliferation, and is particularly important for the establishment of B-cell tolerance.     

Heterogeneity of gangliosides among T cell subsets

Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in TCR-mediated activation. Comprehensive structural analysis of gangliosides in the primary thymocytes and CD4⁺ T and CD8⁺ T cells was not achieved due to technical difficulties. We have found that CD8⁺ T cells express very high levels of o-series gangliosides, but on the other hand, CD4⁺ T cells preferably express a-series gangliosides. In the TCR-dependent activation, CD4⁺ T cells selectively require a-series gangliosides, but CD8⁺ T cells do require only o-series gangliosides but not a-series gangliosides. Ganglioside GM3 synthase-deficient mice lacking a-series gangliosides neither exhibited the TCR-dependent activation of CD4⁺ T nor developed ovalbumin-induced allergic airway inflammation. These findings imply that the distinct expression pattern of ganglioside species in CD4⁺ and CD8⁺ T cells define the immune function of each T cell subset.     

Development of adenocarcinomas after transplantation of rat glandular stomachs treated in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)

Cellular and Molecular Life Sciences - Glandular stomachs of fetal and newborn Wistar rats were transplanted s.c. after treatment in vitro with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) at...     

Effects of adrenal demedullation combined with chemical sympathectomy on cold-induced responses of endocrine pancreas in rats

Adrenal demedullation combined with chemical sympathectomy with 6-hydroxydopamine (ACS) lowered plasma glucagon and insulin levels in rats. Acute cold exposure increased plasma glucagon in both ACS and control rats, while it increased plasma insulin only in ACS rats. ACS rats responded to cold with a smaller increase in plasma glycerol and a more pronounced elevation of plasma free fatty acids.     

Effect of physical exercise on the specific activity of carbonic anhydrase isozyme in human erythrocytes

Summary Significant decreases in the levels of both carbonic anhydrase type B and total esterase activity of human erythrocytes were observed after physical exercise (bicycle ergometer, 150 W for 30 min). Since carbonic anhydrase B-dependent esterase activity likewise decreased, the decrease in the total esterase activity would be caused by the decrease of carbonic anhydrase B activity. The specific activity of carbonic anhydrase B tended to decrease after the exercise. On the other hand no such effects were noted for carbonic anhydrase type C.     

In vivo lipolytic action of glucagon in brown adipose tissue of warm-acclimatized and cold-acclimatized rats

Summary Glucagon infusion caused a marked increase of brown fat venous FFA concentration, but the extent of increase was less in cold-acclimatized rats than in warm-acclimatized ones. Systemic venous FFA was not appreciably influenced by glucagon. Propanolol did not modify the changes induced by glucagon.The authors wish to thank the Novo Industri A/S for the gift of glucagon. — Address of Tomie Ohno: College of School Health, Hokkaido University of Education, Asahikawa 070 (Japan).