The effects of high cholesterol/high fat diet on endoplasmic reticulum stress and neuronal dysfunction in the hippocampus and cerebral cortex of APOE-/- MICE

Mengi, Naz
Hyperlipidemia is an obesity-associated lipid metabolism disorder with high serum total cholesterol (TC) levels and is known to be a risk factor for neurodegenerative diseases. High-fat diet (HFD) induced elevated inflammation levels accompanied by increased levels of apoptosis markers and decreased levels of synaptic proteins in the hippocampus points out a possible neuronal loss. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway is activated by endoplasmic reticulum (ER) stress. The activation of PERK pathway results in reduced protein synthesis and increased expression of transcription factors involved in the apoptotic and inflammatory response. A possible impact of PERK pathway activation on neuronal failure has been questioned. In this study, the impacts of high cholesterol/high-fat diet (HC/HFD) on the PERK pathway, inflammation, postsynaptic integrity, and neurogenesis were investigated in the hippocampus and the cerebral cortex of ApoE-/- mice by performing Western blot analysis. In the hippocampus, no changes in the PERK pathway was detected, inflammation levels were decreased with Western diet. In the cerebral cortex, the levels of ER stress, inflammation, and postsynaptic integrity proteins were significantly increased in ApoE-/- mice independently of the diet. Neurogenesis was significantly higher in the hippocampus and the cerebral cortex of ApoE-/- mice. Whereas there was no effect of HC/HFD on ER stress in the hippocampus, genotype effect activated the PERK pathway in the cerebral cortex.


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Hyperlipidemia is characterized by elevated total cholesterol levels in the circulation, and it is often associated with co-occurrence of neuronal dysfunction and subsequent neurodegeneration. Hyperlipidemia-induced inflammation, synaptic damage and neuronal loss in hippocampus as well as in other regions of the brain consequently leads to cognitive decline. Due to its role in protein translation and cell fate determination, PKR-like endoplasmic reticulum kinase (PERK) arm of the Endoplasmic Reticulum (ER) ...
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Citation Formats
N. Mengi, “The effects of high cholesterol/high fat diet on endoplasmic reticulum stress and neuronal dysfunction in the hippocampus and cerebral cortex of APOE-/- MICE,” Thesis (M.S.) -- Graduate School of Natural and Applied Sciences. Molecular Biology and Genetics, Middle East Technical University, 2019.