Plasticity in eye movement control

The cerebellum plays an important role in the recalibration and adaptive adjustment of movements, as well as learning new motor skills and motor related associations. In this thesis, we investigated the mechanisms underlying cerebellar motor learning. To obtain a better understanding, in how the cerebellum processes and stores information, we used specific perturbations that affected the information processing of the cerebellum. Signal transduction pathways were affected that were considered important for cerebellar motor learning by using genetic tools (transgenic mice) and the application of antibodies. Alterations in cerebellar motor learning were studied by monitoring the oculomotor system of these transgenic and treated mice

Impairment of LTD and cerebellar learning by Purkinje cell–specific ablation of cGMP-dependent protein kinase I

The molecular basis for cerebellar plasticity and motor learning remains controversial. Cerebellar Purkinje cells (PCs) contain a high concentration of cGMP-dependent protein kinase type I (cGKI). To investigate the function of cGKI in long-term depression (LTD) and cerebellar learning, we have generated conditional knockout mice lacking cGKI selectively in PCs. These cGKI mutants had a normal cerebellar morphology and intact synaptic calcium signaling, but strongly reduced LTD. Interestingly, no defects in general behavior and motor performance could be detected in the LTD-deficient mice, but the mutants exhibited an impaired adaptation of the vestibulo-ocular reflex (VOR). These results indicate that cGKI in PCs is dispensable for general motor coordination, but that it is required for cerebellar LTD and specific forms of motor learning, namely the adaptation of the VOR

Chemopreventive effect of flavonoids from Ougan (Citrus reticulata cv. Suavissima) fruit against cancer cell proliferation and migration

Citrus reticulata cv. Sucruissima (Ougan) is a rich source of flavonoids, and its peel has been employed as a traditional Chinese medicine for a long time. Among the different fruit parts, namely flayed, albedo, segment membrane and juice sacs, flavedo showed significant inhibitory effect on three cancer cell lines (HepG2, HL-60 and MDA-MB-231). Three flavanone glycosides, naringin, hesperidin, neohesperidin as well as four polymethoxylated flavones (PMFs), sinensetin, nobiletin, tangeretin and 5-demethylnobiletin were separated and purified from Ougan flavedo and identified by HPLC-DAD and LC-MS. Cytotoxicity assay showed that two flavanone aglycones and four PMFs exhibited significant antiproliferative activity on the three cancer cells. Structure-activity relationship was observed for the Ougan flavonoid-mediated antiproliferative activity. Wound healing assay showed that nobiletin and tangeretin exerted inhibitory effects on SKOV3 cell migration as well. These results indicate that Ougan flavonoids may have preventive or therapeutic potential for inhibiting cancer cell proliferation and migration. (C) 2014 Elsevier Ltd. All rights reserved

Individual Differences in the Accuracy of Judgments of Learning Are Related to the Gray Matter Volume and Functional Connectivity of the Left Mid-Insula

The judgment of learning (JOL) is an important form of prospective metamemory judgment, and the biological basis of the JOL process is an important topic in metamemory research. Although previous task-related functional magnetic resonance imaging (MRI) studies have examined the brain regions underlying the JOL process, the neural correlates of individual differences in JOL accuracy require further investigation. This study used structural and resting-state functional MRI to investigate whether individual differences in JOL accuracy are related to the gray matter (GM) volume and functional connectivity of the bilateral insula and medial Brodmann area (BA) 11, which are assumed to be related to JOL accuracy. We found that individual differences in JOL accuracy were related to the GM volume of the left mid-insula and to the functional connectivity between the left mid-insula and various other regions, including the left superior parietal lobule/precuneus, bilateral inferior parietal lobule/intraparietal sulcus, right frontal pole and left parahippocampal gyrus/fusiform gyrus/cerebellum. Further analyses indicated that the functional connectivity related to individual differences in JOL accuracy could be divided into two factors and might support information integration and selective attention processes underlying accurate JOLs. In addition, individual differences in JOL accuracy were not related to the GM volume or functional connectivity of the medial BA 11. Our findings provide novel evidence for the role of the left mid-insula and its functional connectivity in the JOL process

Oculomotor plasticity during vestibular compensation does not depend on cerebellar LTD

Vestibular paradigms are widely used for investigating mechanisms underlying cerebellar motor learning. These include adaptation of the vestibuloocular reflex (VOR) after visual-vestibular mismatch training and vestibular compensation after unilateral damage to the vestibular apparatus. To date, various studies have shown that VOR adaptation may be supported by long-term depression (LTD) at the parallel fiber to Purkinje cell synapse. Yet it is unknown to what extent vestibular compensation may depend on this cellular process. Here we investigated adaptive gain changes in the VOR and optokinetic reflex during vestibular compensation in transgenic mice in which LTD is specifically blocked in Purkinje cells via expression of a peptide inhibitor of protein kinase C (L7-PKCi mutants). The results demonstrate that neither the strength nor the time course of vestibular compensation are affected by the absence of LTD. In contrast, analysis of vestibular compensation in spontaneous mutants that lack a functional olivocerebellar circuit (lurchers) shows that this form of motor learning is severely impaired. We conclude that oculomotor plasticity during vestibular compensation depends critically on intact cerebellar circuitry but not on the occurrence of cerebellar LTD. Copyrigh

Quantification and Purification of Mangiferin from Chinese Mango (Mangifera indica L.) Cultivars and Its Protective Effect on Human Umbilical Vein Endothelial Cells under H2O2-induced Stress

Mangiferin is a natural xanthonoid with various biological activities. Quantification of mangiferin in fruit peel, pulp, and seed kernel was carried out in 11 Chinese mango (Mangifera indica L.) cultivars. The highest mangiferin content was found in the peel of Lvpimang (LPM) fruit (7.49 mg/g DW). Efficient purification of mangiferin from mango fruit peel was then established for the first time by combination of macroporous HPD100 resin chromatography with optimized high-speed counter-current chromatography (HSCCC). Purified mangiferin was identified by both HPLC and LC-MS, and it showed higher DPPH• free-radical scavenging capacities and ferric reducing ability of plasma (FRAP) than by l-ascorbic acid (Vc) or Trolox. In addition, it showed significant protective effects on human umbilical vein endothelial cells (HUVEC) under H2O2-induced stress. Cells treated with mangiferin resulted in significant enhanced cell survival under of H2O2 stress. Therefore, mangiferin from mango fruit provides a promising perspective for the prevention of oxidative stress-associated diseases

HPLC (280 nm) analysis of HPCE and its different fractions.

<p>A: HPCE; B: The fraction eluted with 40% methanol, F5; C: The fraction eluted with 50% methanol, F6; D: The fraction eluted with 60% methanol, F7; E: The fraction eluted with 100% methanol, F8.</p