Naslov
Novel non-transgenic rat tauopathy model induced by injection of tau oligomers into the entorhinal cortex

Autori
Langer Horvat, Lea ; Španić, Ena ; Babić Leko, Mirjana ; Šimić, Goran

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

Izvornik
Neurologia Croatica 2020 ; 69 (Suppl. 2): 48 / Šimić, Goran ; Mimica, Ninoslav - Zagreb : Denona, 2020, 48-48

Skup
Croatian congress on Alzheimer's disease (CROCAD-20v)

Mjesto i datum
Online, 15.10.2020. - 16.10.2020

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
Alzheimer's disease ; amyloid ; cognitive changes ; entorhinal cortex ; Iba1 ; microglia ; neurofibrillary changes ; rat ; stereotaxy ; tau fibrils ; tau oligomers ; tauopathy

Sažetak
Tau (tubulin-associated unit) is a microtubule- associated protein in neurons. Aberrant assembly of tau proteins into insoluble aggregates produces pathological structures in a number of neurodegenerative diseases, including Alzheimer's disease (AD). Emerging experimental evidence suggests that the spread of tau pathology in the brain in human neurodegenerative disorders reflects the propagation of misfolded tau along neuroanatomically connected brain regions, with the first changes seen in the brainstem and entorhinal cortex from where they propagate to the hippocampus and association neocortical regions. Most of in vivo tau spreading has been shown in mouse transgenic models that overexpress mutated or wild-type human tau. Use of genetic models of familial AD certainly do not represent the complete picture of disease in humans. Thus, other types of animal models relevant to the sporadic form of the disease, which represents over 95% of all AD cases, should be developed. In this study, we aimed to characterize possible pathological changes and trans-synaptic spread of different forms of tau species in 3-4 months old wild-type Wistar rats after a single unilateral injection of tau oligomers or tau fibrils into the medial entorhinal cortex. Our goal was to assess whether tau oligomers and tau fibrils would induce neurofibrillary changes and propagate in a manner similar to AD, and would this tau-related pathology correlate with cognitive impairment. Upon injection of tau fibrils or tau oligomers into the medial entorhinal cortex, we examined the distribution of tau-related changes at different timepoints (4, 8, and 11 months post-injection) using antibodies AT8 and MC1, and the Gallyas silver staining method. Cognitive performance was tested using the open field, the T-maze task, the novel object recognition, and the object-location test. We observed that tau oligomers and tau fibrils exhibit different effects in terms of the ability to propagate tau-related changes. Both variants of inoculated tau proteins rapidly spread via anterograde axonal transport to the hippocampus and parts of the neocortex, including primary motor and somatosensory areas. As we found inoculated tau fibrils and oligomers in the red nucleus and pontine reticular nucleus, we believe that inoculated tau species propagated from cortical pyramidal neurons further through the corticorubral and corticoreticular pathways to the brainstem. The severity of tau changes correlated with impairments in spatial working memory and cognition, as measured by the T-maze spontaneous alternation, the novel object recognition, and the object location test. We concluded that the surprisingly rapid development of cognitive and behavioral changes may represent specific advantage over other existing tauopathy models. Understanding of the role of tau oligomers and tau fibrils in this rat model of neurodegeneration has a good potential for further analyses of mechanisms underlying development and progression of AD and other tauopathies.

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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