IUPUI Research Day 2015

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https://hdl.handle.net/1805/6250
A program book describing the Research Day 2015 events and posters is available from: http://hdl.handle.net/1805/9289.

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Browsing IUPUI Research Day 2015 by Author "Abeysekera, Irushi"

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    Effects of EGCG treatment on deficits in a radial-arm maze spatial pattern separation task in a Down syndrome mouse model
    (Office of the Vice Chancellor for Research, 2015-04-17) Stringer, Megan; Stancombe, Kailey; Gainey, Sean; Sheikh, Zahir; Abeysekera, Irushi; Goodlett, Charles R.; Roper, Randall J.
    Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa 21) and results in a constellation of phenotypes that include intellectual disability. Ts65Dn mice, the most extensively studied model of DS, have three copies of approximately half the genes on Hsa 21 and display many of the phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and has increased expression in a number of tissues. Dyrk1a is also found in three copies in Ts65Dn mice, and has been shown to be involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea, is an inhibitor of Dyrk1a activity. We have previously shown that a three week treatment with EGCG normalizes skeletal abnormalities in Ts65Dn mice. Previous work has found that Ts65Dn mice are significantly impaired in several hippocampal-dependent tasks, including the Morris water maze and novel object recognition. Another hippocampal-dependent process, pattern separation, is the ability to differentiate between similar memories acquired during learning. Distinctive encoding of these similar memories in hippocampal formation is thought to be necessary to distinguish between them. Experimental reductions in adult neurogenesis have produced impairments in pattern separation performance. Given that recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, we hypothesize that Ts65Dn mice will be impaired in the pattern separation task. Furthermore, we hypothesize that treating Ts65Dn mice with EGCG throughout task learning would improve performance to control levels. A radial arm maze-delayed non-matching-toplace pattern separation task with three different degrees of spatial separation is used. Preliminary data suggests that, in contrast to control mice, Ts65Dn mice do not improve their performance over training.
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    Effects of Epigallcatechin-3-gallate in Novel Object Recognition of Ts65Dn Down Syndrome Mice
    (Office of the Vice Chancellor for Research, 2015-04-17) Minhas, Saniya; Abeysekera, Irushi; Delgado, Fatima; Dhillon, Hardeep; Goodlett, Charles R.; Roper, Randall J.
    Down syndrome (DS) is one of the most common genetic disorders and has an incidence of 1/700 births; which can lead to many impairments, both physically and mentally. All individuals with DS have cognitive impairments which results in learning and memory deficits. To study these deficits, we use the Ts65Dn mouse model that carries trisomy of approximately 50% of the genes found on human chromosome 21. DYRK1A, a gene found in three copies in both humans with DS and Ts65Dn mice has been shown to have increased expression in the brains of humans with DS. DYRK1A protein is involved in a number of critical pathways including CNS development. Epigallcatechin-3-gallate (EGCG), the main polyphenolic compound found in green tea, inhibits DYRK1A. We hypothesize that EGCG treatment help improve cognitive deficits in trisomic mice. After treatment, the mice were subjected to behavioral tasks, including the Novel Object Recognition (NOR) test. Our results indicate that there was a significant difference that existed due to trisomy in Ts65Dn mice; but there was no significant effect of a low dose EGCG treatment. Further studies are examining the effects of the NOR task after a higher dose EGCG treatment.
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    Effects of Increased Dosage EGCG Treatment on Cognitive Deficits in the Ts65Dn Down Syndrome Mouse Model
    (Office of the Vice Chancellor for Research, 2015-04-17) Dhillon, Hardeep; Abeysekera, Irushi; Stringer, Megan; Goodlett, Charles R.; Roper, Randall J.
    Down syndrome (DS), caused by trisomy of human chromosome 21 (Hsa21), is the leading genetic cause of cognitive impairment and results in a constellation of phenotypes. Although symptomatic and therapeutic treatments exist for some DS phenotypes, treatments generally do not address the genetic etiology. The Ts65Dn mouse model, which contains a triplication of approximately half the gene orthologs of Hsa21, exhibits hippocampal learning and memory deficits as well as cerebellar motor and spatial deficits similar to those present in individuals with DS. DYRK1A, one of the genes overexpressed in DS, has been identified as a potential cause of cognitive impairment; therefore normalization of DYRK1A activity may be a valid form of treatment. We have shown that Epigallocatechin-3-gallate (EGCG), a major polyphenol of green tea, can rescue skeletal deficits found in the Ts65Dn mouse model at a low dosage. When this same low dosage was used to rescue behavioral deficits, however, it was ineffective. We hypothesize that high dose EGCG treatment lasting throughout the behavioral testing period will rescue the cognitive deficits observed in Ts65Dn mice. Trisomic mice and euploid littermates were given EGCG or water (control) for 7 weeks while being tested sequentially on novel object recognition (NOR) and Morris water maze (MWM). Our current data set shows that Ts65Dn mice exhibit deficits in learning and memory; further data will be collected in order to identify the effect of EGCG. Data showing pure EGCG as being ineffective will suggest the importance adding a supplemental compound, while data showing pure EGCG as an effective form of treatment will strongly support use of EGCG in translational studies in individuals with Down syndrome.
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    Extended Treatment with a High Dosage of EGCG to Rescue Appendicular Bone Abnormalities in a Down Syndrome Mouse Model
    (Office of the Vice Chancellor for Research, 2015-04-17) Singh, Prabhjot; Roper, Randall J.; Abeysekera, Irushi
    Individuals with Down syndrome (DS) show significant abnormalities in cognitive abilities, muscle tone, and bone homeostasis. DS is caused by a triplication of the 21st human chromosome (Hsa21). Previous research conducted by our lab using mouse models indicates that three copies of Dyrk1a causes the appendicular skeletal deficits associated with DS. Ts65Dn mouse model carries 50% of the genes homologous to Hsa21, and exhibit excellent phenotypic model for the skeletal deficits seen in individuals with DS, such as low bone mineral density, altered bone structure, and decreased cortical bone. Epigallocatechin-3-gallate (EGCG) is a green tea polyphenol that inhibits Dyrk1a activity. In a previous study, we showed that a three-week, low dose (10mg/kg/day) treatment of EGCG rescued bone mineral density, and trabecular bone to that of euploid levels, but not cortical bone. We hypothesize that increasing the concentration and duration of the treatment will be sufficient enough to more fully restore bone abnormalities by rescuing femoral bone mineral density, bone volume, and improving overall bone strength. This project explores the effects of using a prolonged seven-week, high dosage (100mg/kg/day) treatment on specific bone phenotypes. Dual Energy X-ray absorptiometry (DXA), MicroCT, and mechanical testing will be used as our means of analysis of the treated and untreated bones.