| Abstrakt: |
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 Ube3amice. Here, we investigate cognitive phenotypes of Ube3amice 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 Ube3amice, 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 Ube3amice, 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 Ube3amice 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. |
