IUPUI Research Day 2014

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https://hdl.handle.net/1805/4256
A program book describing the Research Day 2014 events and posters is available from: http://hdl.handle.net/1805/4257.

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Browsing IUPUI Research Day 2014 by Author "Abeysekera, Irushi S."

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    Effects of Epigallocatechin-3-gallate Treatment on Cognitive Deficits in a Down Syndrome Mouse Model
    (Office of the Vice Chancellor for Research, 2014-04-11) Dhillon, Hardeep; Abeysekera, Irushi S.; Stringer, Megan
    Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in a constellation of phenotypes that include intellectual disability (ID) and skeletal abnormalities. Ts65Dn mice, the most extensively studied model of DS, have three copies of approximately half the genes on Hsa21 and display many DS related phenotypes including skeletal and ID deficits. DYRK1A is found in three copies both in humans with DS and in Ts65Dn mice; DYRK1A has increased expression in humans with DS and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallcatechin-3-gallate (EGCG), the main polyphenolic compound found in green tea, inhibits Dyrk1a activity, and we have shown previously that a three-week treatment with EGCG during adolescence normalizes some skeletal abnormalities in Ts65Dn mice. The current study tested the hypothesis that a similar 3-week treatment with EGCG will also rescue cognitive deficits observed in Ts65Dn mice. Trisomic mice and euploid littermates were given EGCG or water (control) for three weeks during adolescence. Following termination of the treatment, the mice were tested sequentially (over 5 weeks) on locomotor activity (two daily 30-min sessions in an activity chamber), novel object recognition (NOR) memory, acquisition of delayed non-matching to place (DNMP) spatial working memory in a tmaze, or spatial learning and memory in the Morris water maze (MWM). Results to date indicate that Ts65Dn mice exhibit deficits in the learning and memory tasks compared to controls, but the 3-week EGCG treatment did not significantly improve their performance.We hypothesize that for EGCG to be effective for improving cognitive deficits of the Ts65Dn mice, it needs to be present in the brain during the behavioral testing period; our ongoing studies are testing this with continuous EGCG treatment throughout the behavioral testing process.
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    EGCG from different sources: differential stability and effects on treating bone phenotypes related to Down syndrome
    (Office of the Vice Chancellor for Research, 2014-04-11) Thomas, Jared R.; Abeysekera, Irushi S.; Blazek, Joshua D.; Roper, Randall J.
    Down Syndrome (DS) is a genetic disorder caused by trisomy of human chromosome 21 (Hsa21). DS phenotypes include cognitive impairment, craniofacial abnormalities, low muscle tone, and skeletal deficiencies. The Ts65Dn mouse model exhibits similar phenotypes as found in humans with DS, including deficits in skeletal bone. Over-expression of DYRK1A, a serine-threonine kinase encoded on Hsa21, has been linked to deficiencies in DS bone homeostasis. Epigallocatechin-3-gallate (EGCG), an aromatic polyphenol found in green tea (GT), is a known inhibitor of Dyrk1a activity. Normalization of Dyrk1a activity by EGCG may have the potential to regulate bone homeostasis, by increasing bone mineral density (BMD) and bone strength. We hypothesized that EGCG obtained from different vendors would differ in stability as well as success in ameliorating skeletal deficiencies. EGCG from different sources was subjected to degradation analysis because of its low bioavailability due to strong antioxidative characteristics. We also hypothesized that phosphoric acid would stabilize EGCG and prevent breakdown in an aqueous solution. We performed High Performance Liquid Chromatography–Mass Spectrometry (HPLC-MS) on EGCG from different sources to determine the amount of EGCG degradation in solution. Our analyses showed differential stability in EGCG from different sources or with phosphoric acid. We chose EGCG from three sources to test the hypothesis that these compounds would have differing effects treating bone phenotypes associated with DS. Three-week-old Ts65Dn and control male mice were treated with EGCG for three weeks. At six weeks of age, mice were sacrificed and femurs were extracted. BMD, bone strength, as well as architecture of the femur were assessed. Our results indicate that EGCG from different sources has diverse effects on the correction of bone phenotypes associated with DS. Our work is important to understand how EGCG from different sources may affect DS phenotypes as the EGCG is translated to human use.
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    EGCG Treatment on Ts65Dn Mice Suggests a Possible Correlation in Cognitive Development Deficit Reduction
    (Office of the Vice Chancellor for Research, 2014-04-11) Taboada, Maria Fatima Delgado; Abeysekera, Irushi S.; Roper, Randall J.
    Down syndrome (DS) is caused by trisomy of human chromosome 21 (Ts21), affecting 1 in 700 live births. Ts21 results in about 80 phenotypes of which intellectual disability (ID) is one of the most debilitating. DYRK1A, found in 3 copies in individuals with Ts21 has been linked to alterations in morphology and function of the brain resulting in ID. Epigallocatechin-3-gallate (EGCG), a specific inhibitor of Dyrk1a activity has been hypothesized as a possible treatment for the overexpression of this gene, reducing the deficits caused by Dryk1a. Using the Ts65Dn mouse model, we examined the effects on hippocampal dependent learning and memory in the novel object recognition task (NOR) using mice of 3-6 weeks of age (adolescent mice). They were given free access to EGCG (0.124 mg/mL) in their drinking water for 21 days. They were then tested for cognitive improvement through NOR. Ts65Dn and control mice (treated and untreated) were subjected to 3 days of testing with 15 minute sessions per day consisting of habituation, exposure, and test day. All procedures were recorded and analyzed to determine time spent exploring novel object in relation to familiar. Our current results suggest that s65Dn mice do not spend as much time exploring the novel object as euploid mice and there exists a genotype effect, but treatment is not correcting the learning and memory deficit. We hypothesize that continuous EGCG treatment may be needed in order to see cognitive deficit reduction in adolescent mice.