Clonidine reverses spatial learning deficits and reinstates theta frequencies in rats with partial fornix section.

Rats received knife-cuts to the dorsal fornix or sham-operations. Half of the animals from each group were injected with clonidine (0.01 mg/kg) and the others with saline before each daily trail of a 10-trial radial 8-arm maze task. The number of choices before the first repetition and the run time were used as performance indices. Lesioned rats were significantly impaired in the acquisition of this task. Clonidine-treated rats, lesioned or not, had an acquisition profile indistinguishable from that of sham-operated saline-injected rats, in spite of their increased run time. When tested one week after the last learning trial in a no-drug condition, lesioned rats treated with clonidine throughout learning maintained a high level of performance during the 5-day retraining phase. A parallel analysis of theta rhythms recorded in an independent group of rats placed in equivalent treatment and/or lesion conditions was then performed. Preoperatively, clonidine injections decreased theta frequency during both alert immobility and movement. Partial fornix lesions produced an increase in theta frequency. Finally, clonidine in fornix-damaged rats decreased theta frequency, thus reinstating the postoperative values at a level statistically no different from that recorded preoperatively. The role of clonidine in restoring the function of the septo-hippocampal input in partially fornix-damaged rats through a noradrenergic modulation of hippocampal acetylcholine release is discussed.     

Parallel modifications of spatial memory performances, exploration patterns, and hippocampal theta rhythms in fornix-damaged rats: reversal by oxotremorine

Learning scores and degrees of divergence of the exploratory patterns (EP) displayed during the acquisition stage of a radial eight-arm maze task were examined in fornix-damaged and sham-operated rats injected either with oxotremorine (0.1 mg/kg) or saline. Modifications of hippocampal rhythmic slow activity (theta) recorded in each condition were analyzed in CA1 and dentate gyrus. Dorsal fornix sections reduced choice accuracy but also induced the adoption of weakly divergent EP. Oxotremorine in animals with lesions reinstates both learning scores and degree of divergence of EP at the levels respectively observed in saline sham-operated animals. Finally, oxotremorine in sham-operated animals did not significantly improve choice accuracy but strongly modified the EP. Preoperatively, theta rhythms indicated a decrease of frequency after oxotremorine administration. Postoperatively, they showed an increase of frequency in animals with lesions that were reinstated at the preoperative level by oxotremorine.     

Body protein and lipid deficit in tumour-bearing rats in relation to age.

Cancer cachexia is among the most dramatic situations of depletion in body energy reserves. To ascertain whether the pattern of body composition alteration during tumour development is influenced by aging as in uncomplicated starvation, we compared the difference of body composition between Yoshida sarcoma bearing rats and young (200 g, 7 weeks) and adult (400 g, 13 weeks) control rats. After the same duration of tumour bearing, mass and composition of tumours were similar in adult and young rats, indicating that they are independent of host age. Food intake decreased to a remarkably similar value in both young and adults. Body water content was elevated in hosts of both ages. The relative deficit of body lipid vs controls was similar for both, the absolute lipid deficit being therefore larger in adult than in young tumour-bearing rats (14.3 +/- 4.4 g vs 6.8 +/- 0.9 g; P < 0.01). In contrast, there was a relatively larger deficit of body protein in young rats. Paradoxically, these rats still maintained a positive nitrogen balance whereas this balance was negative in adult tumour-bearing rats. In conclusion, as previously shown in uncomplicated undernutrition, the anorexia induced by Yoshida sarcoma development is still associated with some protein accretion in young rats whereas cachexia develops in adults.     

Low molecular weight chitosan inhibits obesity induced by feeding a high-fat diet long-term in mice

Three low molecular weight chitosans (molecular weight: 21, 46 and 130 kDa) obtained by enzymatic hydrolysis of a high molecular weight chitosan (average molecular weight: 650 kDa) had low viscosity and were water-soluble. The effects of these water-soluble chitosans on pancreatic lipase (in-vitro) and the elevation of plasma triacylglycerol concentration after the oral lipid tolerance test were examined in mice. The water-soluble 46-kDa chitosan was the most effective at inhibiting pancreatic lipase activity (in-vitro) and plasma triacylglycerol elevation after the oral lipid tolerance test. Based on this result, the effects of the 46-kDa chitosan on increases in bodyweight, various white adipose tissue weights, and plasma and liver lipids were examined in mice fed a high-fat diet for 20 weeks. Water-soluble 46-kDa chitosan (300 mg kg(-1), twice daily) prevented increases in bodyweight, various white adipose tissue weights and liver lipids (cholesterol and triacylglycerol) in mice fed a high-fat diet, and further increased the faecal bile acid and fat. The results suggest that the lipid-lowering effects of the 46-kDa chitosan may be mediated by increases in faecal fat and/or bile acid excretion resulting from the binding of bile acids, and by a decrease in the absorption of dietary lipids (triacylglycerol and cholesterol) from the small intestine as a result of the inhibition of pancreatic lipase activity. Water-soluble 46-kDa chitosan (100 and 300 mg kg(-1), twice daily) did not cause liver damage with the elevation of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, or kidney damage with the elevation of blood nitrogen urea. It was concluded that water-soluble 46-kDa chitosan is a safe functional food.     

Colonic hyperalgesia triggered by proteinase-activated receptor-2 in mice: involvement of endogenous bradykinin

Intracolonic (i.col.) administration of the PAR2-activating peptide (PAR2AP) SLIGRL-NH2 slowly develops visceral hypersensitivity to i.col. capsaicin in ddY mice. Thus, we further analyzed roles of PAR2 in colonic hypersensitivity, using the novel potent PAR2AP, 2-furoyl-LIGRL-NH2 and PAR2-knockout (KO) mice. In ddY mice, i.col. 2-furoyl-LIGRL-NH2 produced delayed (6 h later) facilitation of capsaicin-evoked visceral nociception, an effect being much more potent than SLIGRL-NH2. Such effects were mimicked by i.col. trypsin. In wild-type (WT), but not PAR2-KO, mice of C57BL/6 background, i.col. PAR2 agonists caused delayed facilitation of sensitivity to capsaicin. The PAR2-triggered visceral hypersensitivity was abolished by a bradykinin B2 receptor antagonist, HOE-140. Our data thus provide ultimate evidence for role of PAR2 in colonic hypersensitivity, and suggest involvement of the bradykinin-B2 pathway.     

Haploinsufficiency of C2GnT-I glycosyltransferase renders T lymphoma cells resistant to cell death

Neoplastic T cells in mycosis fungoides (MF) are resistant to apoptotic agents, including galectin-1 that is abundant in skin. Although MF cells are typically CD7-, and thus galectin-1 resistant, CD7+ HH cells, derived from a patient with MF, were also resistant to galectin-1. HH cells demonstrate altered cell surface glycosylation, with loss of core 2 O-glycan ligands for galectin-1 created by core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT-I). Loss of core 2 O-glycans on tumor cells was also seen in primary CD7+ MF lesions. Surprisingly, HH cells are heterozygous for a C2GnT-I point mutation, yet this mutation resulted in a dramatic reduction in cellular glycosyltransferase activity. Expression of wild-type C2GnT-I in human HH cells, or murine lymphoma cells that lack C2GnT-I, restored core 2 O-glycan expression and susceptibility to galectin-1, whereas mutant enzyme lacked activity and did not restore core 2 O-glycan expression or susceptibility to galectin-1. Mutant enzyme did not have a dominant negative effect by affecting dimerization or activity of wild-type enzyme; rather, C2GnT-I haploinsufficiency is sufficient for loss of core 2 O-glycan expression and galectin-1 resistance. Thus, glycosyltransferase haploinsufficiency results in altered cellular glycosylation and resistance to cell death, identifying a new survival mechanism for T-lymphoma cells.     

Antibiotic susceptibility and molecular diversity of Bacillus anthracis strains in Chad: detection of a new phylogenetic subgroup

We genotyped 15 Bacillus anthracis isolates from Chad, Africa, using multiple-locus variable-number tandem repeat analysis and three additional direct-repeat markers. We identified two unique genotypes that represent a novel genetic lineage in the A cluster. Chadian isolates were susceptible to 11 antibiotics and free of 94 antibiotic resistance genes.     

In Vivo and In Vitro Treatment With Edaravone Promotes Proliferation of Neural Progenitor Cells Generated Following Neuronal Loss in the Mouse Dentate Gyrus

Edaravone is clinically used in Japan for treatment of patients with acute cerebral infarction. To clarify the effect of edaravone on neurogenesis in the hippocampus following neuronal injury in the hippocampal dentate gyrus, we investigated the effect of in vitro and in vivo treatment with edaravone on the proliferation of neural stem/progenitor cells prepared from the mouse dentate gyrus damaged by trimethyltin (TMT). Histological assessment revealed the presence of large number of nestin(+) cells in the dentate gyrus on days 3 – 5 post-TMT treatment. We prepared cells from the dentate gyrus of naïve, TMT-treated mice or TMT/edaravone-treated mice. The cells obtained from the dentate gyrus of TMT-treated animals were capable of BrdU incorporation and neurosphere formation when cultured in the presence of growth factors. The TMT-treated group had a larger number of nestin(+) cells and nestin(+)GFAP(+) cells than the naïve one. Under the culture condition used, sustained exposure of the cells from the damaged dentate gyrus to edaravone at 10^?11 and 10^?8 M promoted the proliferation of nestin(+) cells. The systemic in vivo treatment with edaravone for 2 days produced a significant increase in the number of nestin(+) cells among the cells prepared from the dentate gyrus on day 4 post-TMT treatment, and as well as one in the number of neurospheres formed from these cells in the culture. Taken together, our data indicated that edaravone had the ability to promote the proliferation of neural stem/progenitor cells generated following neuronal damage in the dentate gyrus.