EFFECTS OF DIFFERENT DIETS IN A MOUSE MODEL OF NEURODEGENERATIVE DISEASE
Creators: name: BUCCARELLO, LUCIA
Publisher: name: Universit� degli Studi di Milano
Year: 2015

description: Effects of different diets in a mouse model of neurodegeneration Abstract Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal Tau protein leading to cognitive and/or motor dysfunction; several studies suggest that dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. The mouse model chosen for this study was P301L; mice expressing P301L mutant Tau mimics features of human tauopathies and provides a model for investigating the neuropathogenesis of diseases. In this study we investigate at 7 and 15 months of age the effects of different diets (high fat-protein diet and low fat-protein diet) on P301L TG and CTR mice valuating metabolic, behavioral and cognitive activities; for the metabolic activities we analyzed survival rate, body weight gain and food and water consumption of animals. For behavioral activities we valuated mnemonic, locomotor and exploratory performances of animals; for cognitive activities we investigated the cognitive impairment (identifying agglomerates of hyperphosphorylated tau, neuronal loss, astrogliosis and oxidative damage) using immunohistochemical analysis and neuronal counts. We characterized P301L TG mouse model (trial 1-3) that replicated the impairments found in patients affected by tauophaty in a way age-gender-dependent showing in female TG mice a strong cognitive impairment strictly correlated with an increase in P-Tau, in both cerebral cortex and hippocampus, as well as astrogliosis and oxidative damage. We found an improvement of pathological conditions in TG mice administrating a low fat-protein diet in a way age-gender-dependent (trial 2-3), occurred with an increased lifespan, a reduction of food and water consumption, a reduction of aggregates of P-Tau, neuronal loss, astrogliosis and oxidative damage. We found an interaction between tauophaty and consumption of high fat-protein expressed on peripheral organs as hepatic insulin resistance and fatty accumulation in the liver, which induced nonalcoholic fatty liver disease in TG mice (trial 4). The correlation between P-Tau, insulin/IGF resistance and high fat-protein diet consumption was expressed by a condition of hepatomegaly characterized by the presence of lobular inflammatory infiltrate and deposits of collagen in liver and spleen, an increase of weight and size of liver and spleen, the highest increase of median levels of triglycerides, AST and ALT in P301L TG mice fed with high-fat protein diet in a way age-gender-dependent. In summary, we demonstrated the importance of interaction between nutrition and neurodegeneration and the role that different diets can have on the onset and development of tauophaty, obtaining an improvement of pathological conditions administrating a low fat-protein diet. Results obtained in this study suggest that P301L-Tau model could represent a valuable tool to study the role and the mechanisms through hyperphosphorylation and Tau aggregation leading to cognitive and memory impairment. Using the influence of nutrition for preventing or reducing the accumulation of hyperphosphorylated tau in this model could finally lead to the development of preventive potential treatments for tauopathies.