title: Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model.
abstract: Down syndrome (DS) or Trisomy 21 causes intellectual disabilities in humans and the Ts65Dn DS mouse model is deficient in learning and memory tasks. DYRK1A is triplicated in DS and Ts65Dn mice. Ts65Dn mice were given up to ~20mg/kg/day epigallocatechin-3-gallate (EGCG), a Dyrk1a inhibitor, or water beginning on postnatal day 24 and continuing for three or seven weeks, and were tested on a series of behavioral and learning tasks, including a novel balance beam test. Ts65Dn as compared to control mice exhibited higher locomotor activity, impaired novel object recognition, impaired balance beam and decreased spatial learning and memory. Neither EGCG treatment improved performance of the Ts65Dn mice on these tasks. Ts65Dn mice had a non-significant increase in Dyrk1a activity in the hippocampus and cerebellum. Given the translational value of the Ts65Dn mouse model, further studies will be needed to identify the EGCG doses (and mechanisms) that may improve cognitive function.
authors.affiliation: Department of Psychology, IUPUI, 402 North Blackford Street, LD 124, Indianapolis, IN 46202-3275, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Stringer
authors.affiliation: Department of Biology, IUPUI, 723 West Michigan Street, SL 306, Indianapolis, IN 46202-3275, United States.
authors.forename: Irushi
authors.initials: I
authors.lastname: Abeysekera
authors.affiliation: Department of Chemistry and Chemical Biology, IUPUI, 402 North Blackford Street, LD 326, Indianapolis, IN 46202-3275, United States.
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Dria
authors.affiliation: Department of Biology, IUPUI, 723 West Michigan Street, SL 306, Indianapolis, IN 46202-3275, United States. Electronic address: rjroper@iupui.edu.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Roper
authors.affiliation: Department of Psychology, IUPUI, 402 North Blackford Street, LD 124, Indianapolis, IN 46202-3275, United States.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Goodlett
mesh_terms: D000375:Aging / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology*; D004314:Down Syndrome / Q000150:complications / Q000523:psychology*; D005260:Female; D006128:Growth / Q000187:drug effects; D007858:Learning / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D000097603:Dyrk Kinases
chemical_list: D002392:Catechin; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C045651:epigallocatechin gallate
keywords: Cognition; Down syndrome; Mouse model; Treatment; Trisomy 21