Rapid development of tolerance to the behavioural actions of cholecystokinin

Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.     

Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice

Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showing cerebellar Purkinje cell (PC) loss, and isolated cerebellar injury has been associated with a higher incidence of ASDs. However, the extent of cerebellar contribution to the pathogenesis of ASDs remains unclear. Tuberous sclerosis complex (TSC) is a genetic disorder with high rates of comorbid ASDs that result from mutation of either TSC1 or TSC2, whose protein products dimerize and negatively regulate mammalian target of rapamycin (mTOR) signalling. TSC is an intriguing model to investigate the cerebellar contribution to the underlying pathogenesis of ASDs, as recent studies in TSC patients demonstrate cerebellar pathology and correlate cerebellar pathology with increased ASD symptomatology. Functional imaging also shows that TSC patients with ASDs display hypermetabolism in deep cerebellar structures, compared to TSC patients without ASDs. However, the roles of Tsc1 and the sequelae of Tsc1 dysfunction in the cerebellum have not been investigated so far. Here we show that both heterozygous and homozygous loss of Tsc1 in mouse cerebellar PCs results in autistic-like behaviours, including abnormal social interaction, repetitive behaviour and vocalizations, in addition to decreased PC excitability. Treatment of mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioural deficits. These findings demonstrate new roles for Tsc1 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.     

Galanin – 25 years with a multitalented neuropeptide

The neuropeptide galanin and its receptors are localized in brain pathways mediating learning and memory. Central microinjection of galanin impairs performance of a variety of cognitive tasks in rats. Transgenic mice overexpressing galanin display deficits in some learning and memory tests. The inhibitory role of galanin in cognitive processes, taken together with the overexpression of galanin in Alzheimer's disease, suggests that galanin antagonists may offer a novel therapeutic approach to treat memory loss in Alzheimer's patients.     

椭圆齿旋流口平带传热管内自动清洗及其传热强化

介绍了一种特殊结构的旋流口椭圆齿平带的研制。平带上的每个椭圆齿都是使平带自转的流体动力结构元素,平带两侧的旋流口结构能够使管内的部分液体形成螺旋线流,因而具有近似斜齿纽带那样能够在较低流速下自转实现管内污垢在线自动清洗的宝贵性能。由于椭圆齿后的大量涡流、管内部分液体流线转变为螺旋线流股以及螺旋线流股与轴向流股分合交错这样3方面的作用,管内的对流传热强化的幅度由此远远高于光滑纽带。试验结果表明,这种平带不仅容易制造,并且综合性能好,在管内流速0.5m/s左右就可运行;管内侧的传热系数提高170%,流体阻力在一般工程许可的范围内,因此具有较高的工程应用价值。