Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Topography of median eminence somatostatinergic innervation

Somatostatin (SRIF) in the central nervous system is mostly concentrated in the median eminence (ME). Immunocytochemical methods have revealed high densities of SRIF-positive perikarya between the preoptic area and the periventricular nucleus of the hypothalamus (NPE). The aim of the present study was to define more precisely the specific pathways of SRIF neurons from NPE to the ME. SRIF levels were measured by radioimmunoassay, following various hypothalamic transections. Frontal periventricular sections decreased SRIF-ME content by 70% (P less than 0.01), when located at the anterior end of the ME but no diminution was observed when the cuts were located anteriorly or posteriorly. Parasaggital transections decreased SRIF-ME levels by 50% (P less than 0.05) when located at the outer border of the ventromedial and premammillary nucleus, but the decrease was not significant when cuts were located anteriorly. Taken together, our data indicate that most SRIF-containing neurons, originating in the NPE, do not reach the ME directly along the border of the 3rd ventricle; instead they form a loop across the medial forebrain bundle before re-entering the mediobasal hypothalamus at the ME level.     

Metabolic response to beet fibre test meals

Test meals with 10.9 g dietary fibre from sugar beet and corresponding control meals were given to eight healthy subjects, aged 67 ± 9 years. The postprandial glucose, triglyceride, hormone and glycerol responses were monitored during 3 hours. After the beet fibre meal the insulin and C-peptide areas were reduced by 28 ( P < 0.01) and 22% ( P > 0.025), respectively, and the somatostatin levels increased by approximately 30% ( P > 0.05). Further, the maximum relative postprandial reduction of plasma glycerol levels was less evident after the fibre-rich meal than after the control meal (36 ± 4% v. 46 ± 4%, P < 0.05). There was no apparent difference in the overall glycaemic response between the meals. The triglyceride levels were similar after both test meals.
Suspension of beet fibre bread given to rats by oro-gastric intubation induced lower blood glucose response than a control bread at 15 and 30 min ( P < 0.001), respectively, but a similar insulin response.
The results suggest an effect of beet fibre on the rate of carbohydrate absorption, expressed as a lower insulin response in the healthy volunteers and a reduced glucose response in the rat.
The mechanism behind this effect in healthy subjects could possibly be mediated by an increased somatostatin response.     

红霉素对犬幽门括约肌压力影响及其与胃动素,生长抑素的关系

为探讨红霉素对犬幽门括约肌的作用及其机理，及其与血浆胃动素，生长抑素的关系。方法采用胃压力测量仪及放射免疫法，同步监测观察了１０条犬静脉滴ＥＭ前后和使用拮抗剂后的幽门压力、血浆ＭＴＬ，ＳＳ的变化，结论：ＥＭ具有增高犬胃幽门压力的作用，其作用机理除与血浆ＭＴＬ有着密切的关系外，血浆ＳＳ也可能共同参与了其调节机制。     

Effects of glucagon-like peptide 1 (7–36 amide) on whole-body protein metabolism in healthy man

The incretin glucagon-like peptide 1 (GLP-1) shows glucose-dependent insulinotropic activity and may exert anabolic effects. Whole-body protein metabolism was assessed by measuring [1-¹³C]-leucine kinetics in 13 healthy volunteers during hyperglycaemic clamping with or without pancreatic clamping (somatostatin infusion) in order to differentiate between insulin-mediated and direct GLP-1 effects. During intact pancreatic secretion leucine flux and leucine oxidation rate as parameters of whole-body protein breakdown decreased markedly after 180 min of synthetic GLP-1 infusion (GLP-1 vs. placebo: P  < 0.003). Indirect calorimetry showed an increase in energy expenditure and CO₂ production during GLP-1 administration ( P  < 0.0005). Plasma insulin increased after 3 h of GLP-1 infusion to 1486 ± 145 pmol L⁻¹ vs. 185 ± 12 pmol L⁻¹ for saline ( P  < 0.0001). When plasma insulin levels were kept constant (GLP-1 vs. saline, NS) during pancreatic clamping, GLP-1 effects on both protein metabolism and energy expenditure were abolished. Thus, GLP-1 infusion in man exerts protein anticatabolic and thermic effects, which are mediated by GLP-1-induced stimulation of insulin secretion.     

大鼠应激性溃疡与胃泌素、胰高血糖素和生长抑素的相关性研究

采用冷束缚法建立大鼠应激性溃疡模型，以探讨胃肠激素与应激性溃疡发病的相关性。实验组置于（４±２）℃环境，３Ｈ，对照组置于（１８±３）℃，３ｈ，分别检测不同时间血清胃泌素、胰高血糖素、生长抑素的水平。结果表明，实验组胃泌素、胰高血糖素水平明显高于对照组，生长抑素水平明显低于对照组。提示胃泌素、胰高血糖素、生长抑素可能从不同的角度参与了应激性溃疡的消长过程。     

大鼠正中隆起及垂体结节区生长抑素免疫阳性成分的分布

应用免疫组织化学方法观察了大鼠正中隆起及垂体结节区内生长抑素免疫阳性成分的分布,新发现:在交叉后区的正中隆起前部内侧带,有少量的生长抑素免疫阳性神经元胞体;少量阳性纤维几乎垂直行向腹侧,有的可达脑膜表面。垂体结节区内可见较密集的生长抑素阳性纤维丛,其上可见较多的膨体;一些纤维同样到达腹侧表面。     

胰腺癌细胞的增殖同膜脂质饱和度,膜胰岛素受体的关系

外源性表皮生长因子(或生长抑素)能促进(或抑制)胰腺癌细胞的增殖。胰腺癌细胞增殖速率的高低与细胞膜脂质饱和度的降、升;与膜胰岛素受体数量的增减密切相关。测定细胞膜脂质饱和度和胰岛素受体数量,是判断胰腺癌增殖状态的灵敏指标,有一定临床价值。     

Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH,an analog of somatostatin,or a combination

Summary Female BDF₁ mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp⁶]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25µg/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40–53% inhibition of tumor volumes, 38–43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp⁶]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp⁶]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.