Impacts of high-fat diet and genotype on blood-brain barrier and synaptic integrity in mouse cerebral cortex: an exploration of perk pathway

buir.advisorAdams, Michelle Marie
dc.contributor.authorŞeker, Büşranur
dc.date.accessioned2024-09-25T11:27:42Z
dc.date.available2024-09-25T11:27:42Z
dc.date.copyright2024-09
dc.date.issued2024-09
dc.date.submitted2024-09-23
dc.descriptionCataloged from PDF version of article.
dc.descriptionThesis (M.S.): Bilkent University, Program of Neuroscience, İhsan Doğramacı Bilkent University, 2024.
dc.descriptionIncludes bibliographical references (leaves 87-103).
dc.description.abstractHigh-fat diet intake can induce hyperlipidemia and result in cognitive decline by causing endoplasmic reticulum stress, decreased blood-brain barrier, and synaptic integrity. The protein kinase R-like endoplasmic reticulum kinase (PERK) pathway is one of the arms of the unfolded protein response, which is activated by endoplasmic reticulum stress. The PERK inhibits the global protein translation while allowing the translation of certain proteins that are involved in inflammation and apoptosis. Due to its apoptotic properties, it is thought that the PERK pathway causes neurodegeneration. To study the effects of hyperlipidemia, a high-fat diet-fed Apoe knock-out mice model (Apoe-/-) is appropriate. Knocking out the Apoe in mice makes the animal model more prone to high-fat diet-induced hyperlipidemia. In the cerebral cortex of these animals, endoplasmic reticulum stress, blood-brain barrier, and synaptic integrity markers are checked at protein and mRNA levels. No changes are observed in the PERK pathway markers besides phosphorylated eukaryotic Initiation Factor 2. Additionally, there is a significant increase in blood-brain barrier marker Claudin-5 levels in Apoe-/- mice fed with a high-fat diet. There is also no significant change in synaptic integrity markers. In the second part, the effects of the PERK pathway inhibition are checked with integrated stress response inhibitor and GSK2606414 in the high-fat diet-fed Apoe-/- mice cerebral cortex. There are no significant alterations in BBB and synaptic integrity when the animals are injected with inhibitors. In conclusion, this study investigates the effects of high-fat diet induced hyperlipidemia in the cerebral cortex of Apoe-/- mice on ER stress, blood-brain barrier, and synaptic integrity. In the cerebral cortex region, the PERK pathway-related ER stress is not observed, and synaptic integrity remained unchanged while the blood-brain barrier is affected. Moreover, the effects of the PERK pathway inhibition are researched, and there is no inhibition effect observed in the cerebral cortex region.
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2024-09-25T11:27:42Z No. of bitstreams: 1 B162726.pdf: 3410293 bytes, checksum: 942924630725daddc680e7517f853488 (MD5)en
dc.description.provenanceMade available in DSpace on 2024-09-25T11:27:42Z (GMT). No. of bitstreams: 1 B162726.pdf: 3410293 bytes, checksum: 942924630725daddc680e7517f853488 (MD5) Previous issue date: 2024-09en
dc.description.statementofresponsibilityby Büşranur Şeker
dc.format.extentxxv, 105 leaves : charts ; 30 cm.
dc.identifier.itemidB162726
dc.identifier.urihttps://hdl.handle.net/11693/115855
dc.language.isoEnglish
dc.subjectHigh fat diet
dc.subjectApoe-/-
dc.subjectMice
dc.subjectER stress
dc.subjectBBB and synaptic integrity
dc.subjectPERK pathway inhibition
dc.titleImpacts of high-fat diet and genotype on blood-brain barrier and synaptic integrity in mouse cerebral cortex: an exploration of perk pathway
dc.title.alternativeYüksek yağlı diyet ile genotipin farenin serebral korteksinde kan-beyin bariyeri ve sinaptik bütünlüğe etkileri: perk yolağının araştırılması
dc.typeThesis
thesis.degree.disciplineNeuroscience
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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