Evaluation of a TrkB Agonist on Spatial and Motor Learning in the "Ube3a" Mouse Model of Angelman Syndrome

Autor/inn/en	Schultz, Maria N.; Crawley, Jacqueline N.
Titel	Evaluation of a TrkB Agonist on Spatial and Motor Learning in the "Ube3a" Mouse Model of Angelman Syndrome
Quelle	In: Learning & Memory, 27 (2020) 9, S.346-354 (12 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1072-0502
DOI	10.1101/lm.051201.119
Schlagwörter	Neurological Impairments; Genetics; Genetic Disorders; Symptoms (Individual Disorders); Animals; Spatial Ability; Therapy; Performance; Age; Psychomotor Skills + Suchen Sie Ihr Suchwort? Neurodegenerative Erkrankung; Humangenetik; Psychiatrische Symptomatik; Animal; Tier; Tiere; Räumliches Vorstellungsvermögen; Therapie; Achievement; Leistung; Alter; Lebensalter; Psychomotorische Aktivität
Abstract	Angelman syndrome is a rare neurodevelopmental disorder caused by a mutation in the maternal allele of the gene "Ube3a." The primary symptoms of Angelman syndrome are severe cognitive deficits, impaired motor functions, and speech disabilities. Analogous phenotypes have been detected in young adult "Ube3a" mice. Here, we investigate cognitive phenotypes of "Ube3a" mice as compared to wild-type littermate controls at an older adult age. Water maze spatial learning, swim speed, and rotarod motor coordination and balance were impaired at 6 mo of age, as predicted. Based on previous findings of reduced brain-derived neurotrophic factor in "Ube3a" mice, a novel therapeutic target, the TrkB agonist 7,8-DHF, was interrogated. Semichronic daily treatment with 7,8-DHF, 5 mg/kg i.p., did not significantly improve the impairments in performance during the acquisition of the water maze hidden platform location in "Ube3a" mice, after training with either massed or spaced trials, and had no effect on the swim speed and rotarod deficits. Robust behavioral phenotypes in middle-aged "Ube3a" mice appear to result from continued motor decline. Our results suggest that motor deficits could offer useful outcome measures for preclinical testing of many pharmacological targets, with the goal of reducing symptoms in adults with Angelman syndrome. (As Provided).
Anmerkungen	Cold Spring Harbor Laboratory Press. 500 Sunnyside Boulevard, Woodbury, NY 11797-2924. Tel: 800-843-4388; Tel: 516-367-8800; Fax: 516-422-4097; e-mail: cshpres@cshl.edu; Web site: http://learnmem.cshlp.org
Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2024/1/01