Povezanost kognitivne sposobnosti s glutamatnom i inzulinskom signalizacijom u štakorskom modelu Parkinsonove bolesti

master's thesis

• Title (english): Association of cognitive ability with glutamate and insulin signaling in a rat model of Parkison's disease
• Author: Marija Piknjač
• Mentor: Ana Knezović (mentor)
• Mentor: Sofia Ana Blažević (sumentor)
• Committee member: Sofia Ana Blažević (predsjednik povjerenstva)
• Committee member: Damjan Franjević (član povjerenstva)
• Committee member: Anamaria Štambuk (član povjerenstva)
• Committee member: Marin Ježić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Parkinsonova bolest, osim što se smatra poremećajem kretanja, može se manifestirati i pojavom kognitivnih poremećaja. U nastanak kognitivnog deficita u Alzheimerovoj bolesti uključeni su poremećaji glutamatne i inzulinske signalizacije. Jedan od glavnih ciljeva ovog rada je istražiti kogniciju štakorskog modela Parkinsonove bolesti, te povezanost s glutamatnom i inzulinskom signalizacijom u mozgu, induciranoga obostranom intrastrijatalnom primjenom 6-hidroksidopamina. 6-hidroksidopamin je toksin koji se koristi za selektivnu depleciju dopaminergičkih neurona. Tri mjeseca nakon primjene 6-hidroksidopamina provedeni su motorički i kognitivni testovi (test rotirajućeg cilindra, Morrisov test plivanja u labirintu, test pasivnog izbjegavanja), te su životinje bile žrtvovane. U regijama mozga (hipokampus, hipotalamus i strijatum) promatrane su promjene ekspresije proteina uključenih u inzulinsku i glutamatnu signalizaciju, te ekspresija tirozin hidroksilaze imunofluorescencijom, Westernskom metodom otiska i enzimskog testa visoke osjetljivosti (ELISA). Tri mjeseca nakon primjene 6-hidroksidopamina uočen je kognitivni i motorički deficit, dok je ekspresija proteina uključenih u inzulinsku signalizaciju ostala uglavnom nepromijenjena. Uz motorički i kognitivni deficit, uočena je smanjena ekspresija tirozin hidroksilaze, te snižena aktivacija AMPAR-a u hipokampusu i strijatumu, dok su dopaminergičke jezgre u supstanciji nigri ostale očuvane. Rezultati upućuju na moguću povezanost disfunkcije glutamatne signalizacije i kognitivnog deficita u štakorskom modelu Parkinsonove bolesti.

Abstract (english)

Parkinson's disease, in addition to being considered a motoric disorder, can be manifested by the appearance of cognitive deficit. Glutamate and insulin signalling dysfunction is involved in the development of cognitive deficit in Alzheimer's disease. One of the main goals of this thesis is to investigate cognition in rat model of Parkinson’s disease, and its association with brain glutamate and insulin signalling, induced by bilateral intrastriatal injection of 6-hydroxydopamine (toxin used for the selective depletion of dopaminergic neurons). Three months after 6-hydroxydopamine treatment, animals were subjected to motoric and cognitive tests (RotaRod, Passive avoidance, Morris Water Maze) and later sacrificed. Expression of tyrosine hydroxylase and proteins involved in insulin and glutamate signalling were assessed in hippocampus, hypothalamus and striatum by immunofluorescence, Western blot and ELISA methods. Cognitive and motor deficit was observed three months after the administration of 6-hydroxydopamine, while protein expression involved in insulin signalling remained largely unchanged. Motor and cognitive deficit were observed as well as a decrease in tyrosine hydroxylase expression and AMPAR activation the hippocampus and striatum, while dopaminergic nuclei in substantia nigra were preserved, suggesting a possible association between glutamate signalling dysfunction and cognitive deficit in a rat model of Parkinson’s disease.

• Keywords: 6-hidroksidopamin; tirozin hidroksilaza; kognitivni deficit; inzulinski signalizacijski put; glutamatni signalizacijski put
• Keywords (english): 6-hydroxydopamine; tyrosine hydroxylase; cognitive deficit; insulin signalling pathway; glutamate signalling pathway
• Language: croatian
• URN:NBN: urn:nbn:hr:217:215842
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-05-28
• Created on: 2021-10-08 11:27:21