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master's thesis
Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša
Rijeka: University of Rijeka, Faculty of Medicine, 2024. urn:nbn:hr:184:740249
Špeh, Gabriela
University of Rijeka
Faculty of Medicine

Institutional repository: Repository of the University of Rijeka, Faculty of Medicine

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Špeh, G. (2024). Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša (Master's thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:740249

Špeh, Gabriela. "Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša." Master's thesis, University of Rijeka, Faculty of Medicine, 2024. https://urn.nsk.hr/urn:nbn:hr:184:740249

Špeh, Gabriela. "Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša." Master's thesis, University of Rijeka, Faculty of Medicine, 2024. https://urn.nsk.hr/urn:nbn:hr:184:740249

Špeh, G. (2024). 'Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša', Master's thesis, University of Rijeka, Faculty of Medicine, accessed 30 November 2024, https://urn.nsk.hr/urn:nbn:hr:184:740249

Špeh G. Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša [Master's thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2024 [cited 2024 November 30] Available at: https://urn.nsk.hr/urn:nbn:hr:184:740249

G. Špeh, "Uloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša", Master's thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:184:740249

Metadata
TitleUloga TDP-43 proteinopatije u razvoju neuroupale i neurodegeneracije u modelu ponavljajuće blage traumatske ozljede mozga u miša
AuthorGabriela Špeh
MentorKristina Pilipović (mentor)
MentorJelena Rajič Bumber (komentor)
GranterUniversity of Rijeka
Faculty of Medicine
Rijeka
Defense date and country2024-09-16, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Clinical Pharmacology and Toxicology
Abstract
Ciljevi israživanja: Istražiti regulaciju TAR DNK vezujućeg proteina 43 (engl. TAR DNA binding protein-43; TDP-43) u frontalnom korteksu, hipokampusu i optičkom traktu u modelu ponavljajuće blage traumatske ozljede mozga (engl. mild traumatic brain injury, mTBI) u miševa divljeg tipa i TDP-43 transgeničnog tipa, te analizirati i usporediti prisutnost i intenzitet neurodegeneracije i aktivaciju glija stanica u navedenim dijelovima velikog mozga. Materijali i metode: Ponavljajuće ozljede mozga izazvane su metodom pada utega, po dvije ozljede dnevno tijekom pet uzastopnih dana. Izražaj proteina od interesa u citoplazmatskim i nuklearnim frakcijama analiziran je Western blot metodom. Imunohistokemijskim analizama praćena je unutarstanična lokalizacija i raspodjela TDP-43 u različitim tipovima stanica. Neurodegeneracija je procijenjena bojanjem Fluoro-Jade C. Rezultati: Ponavljajuća mTBI nije utjecala na razvoj neurodegeneracije u frontalnom korteksu i hipokampusu ozlijeđenih miševa, dok su neurodegenerativne promjene bile prisutne u optičkom traktu. Razlike nisu uočene u intenzitetu Fluoro-Jade C bojenja između miševa različitih genotipova u optičkom traktu. Ponavljajuća mTBI nije imala utjecaj na citoplazmatsku i nuklearnu ekspresiju TDP-43, niti na citoplazmatsku ekspresiju TDP-35 u frontalnom korteksu ozljeđenih miševa oba genotipa. Razine mikroglijalne i astrocitne reakcije između lažno ozlijeđenih miševa i onih s ponavljajućom mTBI u frontalnom korteksu, hipokampusu i optičkom traktu nisu se značajno razlikovale. Zaključak: Ovaj rad pokazuje da nema promjena TDP-43 proteina, kao ni neurodegenerativnih promjena i glijalne aktivacije u frontalnom korteksu i hipokampusu ozlijeđenih miševa, 12 mjeseci nakon ponovljajućih blagih traumatskih ozljeda mozga. Međutim, ponovljajuća mTBI uzrokuje neurodegeneraciju i pojačanu glijalnu reakciju u optičkom traktu, što ukazuje na osjetljivost ove strukture na mTBI. Daljnja istraživanja potrebna su za razumijevanje veze između TDP-43 i oštećenja mozga te za razvoj novih terapija.
Abstract (english)
Objectives: To investigate the regulation of TAR DNA binding protein 43 (eng. TAR DNA binding protein-43; TDP-43) in the frontal cortex, hippocampus and optic tract in a model of repetitive mild traumatic brain injury (eng. mild traumatic brain injury; mTBI) in of wild-type and TDP-43 transgenic mice, and to analyze and compare the presence and intensity of neurodegeneration and glial cell activation in the mentioned parts of the cerebrum. Materials and methods: Repetitive brain injuries were induced by the weight drop method, two injuries per day for five consecutive days. Western blotting analyzed the expression of proteins of interest in cytoplasmic and nuclear fractions. Immunohistochemical analyses followed subcellular localization and distribution of TDP-43 in different cell types. Neurodegeneration was assessed by Fluoro-Jade C staining. Results: mTBI did not affect the development of neurodegeneration in the frontal cortex and hippocampus of injured mice, while neurodegenerative changes were present in the optic tract. No differences were observed in the intensity of Fluoro-Jade C staining between different genotypes in the optic tract. mTBI did not affect the cytoplasmic and nuclear expression of TDP-43, nor the cytoplasmic expression of TDP-35 in the frontal cortex of injured mice of both genotypes. No significant differences were noted in the levels of microglial and astrocytic response between sham-injured mice and those with repetitive mild traumatic brain injury in the frontal cortex, hippocampus, and optic tract. Conclusion: This work shows that changes in TDP-43 are not associated with neurodegeneration or glial activation in the frontal cortex of injured mice, 12 months after repeated mild traumatic brain injury. However, repeated mTBI causes neurodegeneration and increased glial responsiveness in the optic tract, confirming its susceptibility to mTBI. Further research is needed to understand the link between TDP-43 and brain damage and to develop new therapies.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:184:740249
Study programmeTitle: Study of Sanitary Engineering
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra sanitarnog inženjerstva (magistar/magistra sanitarnog inženjerstva)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-09-13 13:00:08