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Impact of different types of antidiabetic interventions on the development of neurodegenerative changes in brains of diabetic mice and rats
Popelová, Andrea ; Maletínská, Lenka (advisor) ; Mareš, Pavel (referee) ; Hölscher, Christian (referee)
Alzheimer's disease (AD) is neurological disorder characterized by extracellular beta amyloid plaques and intracellular neurofibrillary tangles formed by hyper-phosphorylated Tau protein. Since type 2 diabetes mellitus (T2DM) is a risk factor of AD development, in the first part of the thesis, a potential relationship between hyper-phosphorylation of Tau protein and central insulin resistance was followed in hippocampi of two models of obesity-induced pre-diabetes, fa/fa rats, and mice with monosodium glutamate (MSG) induced obesity. In both 8-month-old fa/fa rats and 6-month- old MSG mice a decreased phosphorylation of insulin signaling cascade resulted in an increased activation of main Tau kinase glycogen-synthase kinase-3Beta (GSK-3β) and an increased Tau phosphorylation at epitopes Ser396 and Thr231. This phenomenon was less developed in 2-month-old animals. The second part of the thesis was focused on a potential neuroprotective anorexigenic neuropeptide, prolactin-releasing peptide (PrRP), designed at our Institute. Palmitoylation enabled PrRP to cross the blood-brain barrier and employ its central anorexigenic activity. In the third part of the thesis, an effect of 14-day-long SC administration of liraglutide, the most used anti-T2DM drug with central anorexigenic effect, and palmitoylated...
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Impact of different types of antidiabetic interventions on the development of neurodegenerative changes in brains of diabetic mice and rats
Popelová, Andrea ; Maletínská, Lenka (advisor) ; Mareš, Pavel (referee) ; Hölscher, Christian (referee)
Alzheimer's disease (AD) is neurological disorder characterized by extracellular beta amyloid plaques and intracellular neurofibrillary tangles formed by hyper-phosphorylated Tau protein. Since type 2 diabetes mellitus (T2DM) is a risk factor of AD development, in the first part of the thesis, a potential relationship between hyper-phosphorylation of Tau protein and central insulin resistance was followed in hippocampi of two models of obesity-induced pre-diabetes, fa/fa rats, and mice with monosodium glutamate (MSG) induced obesity. In both 8-month-old fa/fa rats and 6-month- old MSG mice a decreased phosphorylation of insulin signaling cascade resulted in an increased activation of main Tau kinase glycogen-synthase kinase-3Beta (GSK-3β) and an increased Tau phosphorylation at epitopes Ser396 and Thr231. This phenomenon was less developed in 2-month-old animals. The second part of the thesis was focused on a potential neuroprotective anorexigenic neuropeptide, prolactin-releasing peptide (PrRP), designed at our Institute. Palmitoylation enabled PrRP to cross the blood-brain barrier and employ its central anorexigenic activity. In the third part of the thesis, an effect of 14-day-long SC administration of liraglutide, the most used anti-T2DM drug with central anorexigenic effect, and palmitoylated...
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