Taurine Administration Recovers Motor and Learning Deficits in an Angelman Syndrome Mouse Model
2018
Angelman syndrome(AS, MIM 105830) is a rare
neurodevelopmental disorderaffecting 1:10–20,000 children. Patients show moderate to
severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic
gamma-aminobutyric acid(GABA) receptors implicated in the pathogenesis.
Taurineis a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties. As
taurineacts as an agonist of GABA-A receptors, we aimed at investigating whether it might ameliorate AS symptoms. Since mice weaning, we orally administered 1 g/kg/day
taurinein water to
Ube3a-deficient mice. To test the improvement of motor and
cognitive skills, Rotarod, Novel Object Recognition and Open Field tests were assayed at 7, 14, 21 and 30 weeks, while biochemical tests and amino acid dosages were carried out, respectively, by Western-blot and high-performance liquid chromatography (HPLC) on frozen whole brains. Treatment of Ube3am−/p+ mice with
taurinesignificantly improved motor and learning skills and restored the levels of the post-synaptic PSD-95 and pERK1/2-ERK1/2 ratio to wild type values. No side effects of
taurinewere observed. Our study indicates
taurineadministration as a potential therapy to ameliorate motor deficits and learning difficulties in AS.
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