Objective: The aim of this project was to evaluate high-fat diet (HFD) induced behavioral alterations in the A53T alpha-Synuclein Parkinsons’s disease mouse model.

Background: Besides genetic modifications nutrition has been suggested to be involved in the development and progression of Parkinson’s disease (PD) (see references 1-4). To investigate the influence of dietary composition on PD, transgenic mice overexpressing A53T-mutated alpha-Synuclein and non-transgenic littermates were fed a high-fat or control diet (CD) from 3.5 to 12 months of age.

Method: During this treatment period body weight and food consumption were evaluated weekly. Additionally, several assays related to glucose metabolism, motor performance and activity were performed.

Results: Both, A53T-transgenic and non-transgenic mice fed with the HFD gained more weight than animals fed with the CD. Furthermore, both genotypes on a HFD exhibited higher blood glucose levels in the glucose tolerance test as early as 5 weeks of treatment compared to baseline values before treatment start. However, glucose levels returned earlier to baseline in A53T-transgenic mice than in non-transgenic mice. The Rota Rod, Beam Walk and Grip Strength tests revealed deficits in motor coordination and balance as well as muscle strength in HFD-fed A53T-transgenic mice. These results were corroborated by altered locomotor activity in HFD-treated A53T-transgenic animals as observed in the Open Field test. Finally, the Forced Swim test demonstrated that transgene overexpression in combination with HFD resulted in depressive-like behavior.

Conclusion: Summarizing, these findings show that A53T-transgenic and non-transgenic mice respond to the HFD in different ways. We anticipate that this mouse model will be useful to investigate nutritional changes and thus might contribute to a better understanding of diet-induced molecular alterations in PD.

References: 1: Polymeropoulos et al., 1997; Science 276, 2045-7 2: Krüger et al., 1998; Nat Genet. 18, 106-8 3: Zarranz et al., 2004; Ann Neurol., 55, 164-73 4: Ascherio and Schwarzschild, 2016; Lancet Neurol. 15, 1257-1272

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-a-high-fat-diet-on-the-behavior-of-a53t-alpha-synuclein-parkinsons-disease-mice/