Therapeutic effectiveness of levodopa in the treatment of seizures and motor defects using the Angelman Syndrome mouse model
This grant supported a trial of levodopa-carbidopa treatment on AS mice. Levodopa is a dopamine precursor that is converted to dopamine in the brain and is commonly used as a treatment for Parkinson disease. AS mice and normal controls were treated with two different dosages of levodopa-carbidopa or placebo and subjected to tests of motor and cognitive abilities, anxiety and seizure susceptibility. Brain regions were analyzed for Dopamine and other monoamine neurotransmitter levels. Alterations in CAMKII phosphorylation (something that was discovered to be abnormal in the AS mouse model) was also examined. Behavior testing showed an improvement in motor function dependent on treatment, but did not normalize cerebellar-mediated licking behavior. Low-dose levodopa treatment partially rescued motor function but did not completely rescue AS mouse behavioral phenotypes.