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bioRxiv · 10.1101/487629

Exenatide reverts the high-fat-diet-induced impairment of BDNF signaling and inflammatory response in an animal model of Alzheimer’s disease

Bomba, M.·Granzotto, A.·Castelli, V.·Lattanzio, R.·Cimini, A.·Sensi, S. L.
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Abstract

Backgroundpreclinical, clinical, and epidemiological evidence support the notion that Alzheimers disease(AD) is a multifactorial condition in which, along with {beta}-amyloid (A{beta}) and tau-related pathology, the synergistic activity of genetic, environmental, vascular, metabolic, and inflammatory factors promote the onset and progression of the disease. Epidemiological evidence indicate that glucose intolerance, deficits in insulin secretion or type 2 diabetes mellitus (T2DM) participate in increasing the risk of developing cognitive impairment or dementia. A pivotal role in the process is played by insulin as the hormone critically regulates brain functioning. GLP-1, the glucagon-like peptide 1, facilitates insulin signaling, regulates glucose homeostasis, and modulates synaptic plasticity. Exenatide is a GLP-1R agonist, characterized by an extended half-life, employed in T2DM. However, exenatide has also been shown to affect the signaling of the brain-derived neurotrophic factor (BDNF), synaptic plasticity, and cognitive performances in animal models of brain aging and neurodegeneration.\n\nMethodsin this study, we tested whether exenatide exerts neuroprotection in a preclinical AD model set to mimic the clinical complexity of the human disease. To that aim, we investigated the effects of 3-month exenatide treatment in 3xTg-AD mice challenged for six months with a high-fat diet (HFD). Endpoints of the study were variations in systemic metabolism, insulin and neurotrophic signaling, neuroinflammation, levels of A{beta} and tau pathology as well as changes in cognitive performances.\n\nFindings and interpretationresults of the study indicate that exenatide reverts the adverse changes of BDNF signaling and the neuroinflammation status of 3xTg-AD mice undergoing HFD.

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Bomba, M., Granzotto, A., Castelli, V., Lattanzio, R., Cimini, A., Sensi, S. L.. 2018-12-04. Exenatide reverts the high-fat-diet-induced impairment of BDNF signaling and inflammatory response in an animal model of Alzheimer’s disease. https://doi.org/10.1101/487629

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