Therapeutic potential of palmitoylethanolamide in a transgenic animal model of Alzheimer's disease: focus on neuroinflammation and synaptic dysfunction.

The general aim of the proposed study is to validate PEA as a clinical candidate for AD therapy. To this aim, we intend to verify whether chronic (3 months) PEA treatments are able to prevent/slow the age-dependent progression of the pathology in a transgenic animal model of AD [the triple-transgenic murine model of AD (3xTg-AD), which harbors 3 mutant human genes (AβPPSwe, PS1M146V, tauP301L); Oddo et al., 2003]. We also intend to identify an optimal PEA dose and to compare preventive vs therapeutic pharmacological interventions with PEA in AD. To this purposes, presymptomatic (2-3 months of age) and symptomatic (12 months of age) 3xTg-AD mice will be used. The project aims will be accomplished by complementary in vitro and in vivo approaches focusing on age-dependent neuroinflammation (panel of cytokines/chemokines), synaptic dysfunction (acetylcholine and glutamate levels by in vitro synaptosome experiments; synaptophysin and PSD-95 protein levels) and cognitive performances (novel object recognition test, Y-maze test, Barnes maze test).
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Comunicazione assenza 19/10/2015