Naslov
Development of a non-transgenic rat model of tauopathy induced by inoculation of tau protein into the medial entorhinal cortex
(Razvoj netransgenog štakorskog modela tauopatije izazvane inokulacijom tau proteina u medijalni entorinalni korteks)

Autori
Langer Horvat, Lea ; Šimić, Goran

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

Izvornik
Neurologia Croatica 71 (Suppl. 3): 60 / Šimić, Goran ; Mimica, Ninoslav - Zagreb : Denona, 2022, 60-60

Skup
Croatian congress on Alzheimer's disease (CROCAD-22)

Mjesto i datum
Supetar, Hrvatska, 05.10.2022. - 08.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Alzheimer's disease ; cognition ; entorhinal cortex ; experimental model ; neurofibrillary degeneration ; stereotaxic inoculation ; tau protein fibrils ; tau protein oligomers ; Wistar rat
(Alzheimerova bolest ; kognicija ; entorinalna moždana kora ; eksperimentalni model ; neurofibrilarna degeneracija ; stereotaksijska inokulacija ; fibrili tau proteina ; oligomeri tau proteina ; Wistar štakor)

Sažetak
Transgenic mice models have been extensively used in Alzheimer's disease (AD) research, but they are limited in their ability to replicate the complex processes of sporadic AD. In this study, we characterized the trans-synaptic spread of synthetic tau fibrils in a non-transgenic Wistar rat, determined whether tau progression is similar to AD-related changes, and assessed the association of pathological changes of tau protein with cognitive impairment. Tauopathy in the brain of patients with AD starts in the brainstem and transentorhinal cortex and spreads along anatomically connected brain regions. To test whether pathological changes initiated in the entorhinal cortex spread through the brain along synaptically connected circuits, unilateral inoculation of synthetic tau fibrils into the medial entorhinal cortex was performed. The distribution of tau-related changes at different time points (4, 8, and 11 months post-injection) was examined using the AT8 monoclonal antibody (specific for tau phosphorylated at Ser202/Thr205) and the Gallyas silver staining method. The results showed that, in addition to neurofibrillary changes found in the entorhinal cortex and hippocampal formation after 4 months, stereotaxic inoculation of tau fibrils caused the appearance of conformationally altered tau protein, formation of Gallyas-positive inclusions, accumulation of amyloid , loss of synapses, and deficits in spatial working memory and cognition, as measured by the T-maze spontaneous alternation and novel object location tests. Understanding the role and behavior of tau proteins in this rat model of neurodegeneration has great potential for revealing mechanisms underlying the development and progression of AD in the human brain and thus may contribute to future AD preclinical testing and drug discovery.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti, Psihologija, Kognitivna znanost (prirodne, tehničke, biomedicina i zdravstvo, društvene i humanističke znanosti)

Napomena
Rad je dobio prvu nagradu za najbolji poster na kongresu (The first place award for the best poster)

POVEZANOST RADA