Naslov
Inoculation of human tau fibrils and tau oligomers into the medial entorhinal cortex produces a novel non-transgenic rat tauopathy model

Autori
Langer Horvat, Lea ; Španić Popovački, Ena ; Šimić, Goran

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of The Second Annual Meeting of the ProteoCure COST Action / Boban, Mirta - Zagreb : COST Action, 2023, 77-77

Skup
The Second Annual Meeting of the ProteoCure COST Action

Mjesto i datum
Zagreb, Hrvatska, 12.06.2023. - 15.06.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Alzheimer’s disease ; cognition ; neurofibrillary degeneration ; spatial working memory ; tau fibrils ; tau oligomers ; tau protein ; tauopathy model ; Wistar rat

Sažetak
Emerging experimental evidence suggests that misfolded tau is to blame for the spread of pathological tau protein changes in the human brain caused by neurodegenerative disorders, especially Alzheimer's disease (AD). The first lesions happen in the brainstem and entorhinal cortex and then spread to the hippocampus and connected neocortical regions. Most tau spread in living organisms has been seen in transgenic mouse models that overexpress either mutated or wild-type human tau. In this study, we aimed to identify potential neurofibrillary alterations in non-transgenic wild-type Wistar rats following the injection of human tau oligomers and tau fibrils into the medial entorhinal cortex (mEC). Recombinant human tau protein was expressed, purified, and treated with 8 mM urea to obtain monomeric human tau. Oligomers were produced through cross-seeding with A-beta oligomers. After adding A-beta oligomers, the sample was mixed by pipetting and incubated for 1 hour on an orbital shaker at room temperature. A new monomeric tau sample was seeded with purified human tau oligomers. Seeding monomeric human tau with purified human tau oligomers and A-beta oligomers for two cycles got rid of the seeds. Tau fibrils were generated by mixing tau oligomers for 1-2 days on an orbital shaker. We examined the distribution of tau-related alterations at different time points (4, 8, and 11 months after injection) using antibodies. AT8 is used to look at early phosphorylation, MC1 is used to look at tau's abnormal shape, and synaptophysin is used to see if injected tau proteins get into synapses and affect their breakdown. We discovered that tau oligomers and tau fibrils have distinct effects on the ability to propagate tau-related changes. When rats were given human tau fibrils, phosphorylated tau protein at the AT8 epitopes spread throughout the brain as soon as 4 months later. This shows that neurofibrillary degeneration spreads faster than when human tau oligomers are used. The T-maze, new object recognition, and object location tests were used to find out how bad tau changes were after human tau oligomers and tau fibrils were injected. These tests showed that spatial working memory and cognition were affected. This non-transgenic rat model of tauopathy, especially when using human tau fibrils, shows that neuronal and synaptic changes, as well as changes in cognition and behavior, happen quickly. Understanding how tau proteins work in this rat model of neurodegeneration could lead to a better understanding of how Alzheimer's disease develops and spreads in the human brain. This could help with future preclinical testing and drug development for AD.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti), Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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