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Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model
Biomedicines, 11 (2023), 4; 1004. https://doi.org/10.3390/biomedicines11041004
Langer Horvat, Lea; Španić Popovački, Ena; Babić Leko, Mirjana; Zubčić, Klara; Horvat, Luka; Mustapić, Maja; Hof, Patrick R.; Šimić, Goran

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Langer Horvat, L., Španić Popovački, E., Babić Leko, M., Zubčić, K., Horvat, L., Mustapić, M. ... Šimić, G. (2023). Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model. Biomedicines, 11. (4). doi: 10.3390/biomedicines11041004

Langer Horvat, Lea, et al. "Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model." Biomedicines, vol. 11, br. 4, 2023. https://doi.org/10.3390/biomedicines11041004

Langer Horvat, Lea, Ena Španić Popovački, Mirjana Babić Leko, Klara Zubčić, Luka Horvat, Maja Mustapić, Patrick R. Hof i Goran Šimić. "Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model." Biomedicines 11, br. 4 (2023). https://doi.org/10.3390/biomedicines11041004

Langer Horvat, L., et al. (2023) 'Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model', Biomedicines, 11(4). doi: 10.3390/biomedicines11041004

Langer Horvat L, Španić Popovački E, Babić Leko M, Zubčić K, Horvat L, Mustapić M, i sur.. Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model. Biomedicines [Internet]. 24.03.2023. [pristupljeno 04.04.2025.];11(4). doi: 10.3390/biomedicines11041004

L. Langer Horvat, et al., "Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model", Biomedicines, vol. 11, br. 4, Ožujak 2023. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:475072. [Citirano: 04.04.2025.]

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Naslov (engleski)Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model
AutorLea Langer Horvat
AutorEna Španić Popovački
AutorMirjana Babić Leko
AutorKlara Zubčić
AutorLuka Horvat
AutorMaja Mustapić
AutorPatrick R. Hof
AutorGoran Šimić
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Neuroznanost
Sažetak (engleski)
The tauopathy of Alzheimer’s disease (AD) is first observed in the brainstem and entorhinal cortex, spreading trans-synaptically along specific pathways to other brain regions with recognizable patterns. Tau propagation occurs retrogradely and anterogradely (trans-synaptically) along a given pathway and through exosomes and microglial cells. Some aspects of in vivo tau spreading have been replicated in transgenic mice models expressing a mutated human MAPT (tau) gene and in wild-type mice. In... Više this study, we aimed to characterize the propagation of different forms of tau species in non-transgenic 3–4 months old wild-type rats after a single unilateral injection of human tau oligomers and tau fibrils into the medial entorhinal cortex (mEC). We determined whether different variants of the inoculated human tau protein, tau fibrils, and tau oligomers, would induce similar neurofibrillary changes and propagate in an AD-related pattern, and how tau-related pathological changes would correlate with presumed cognitive impairment. We injected human tau fibrils and tau oligomers stereotaxically into the mEC and examined the distribution of tau-related changes at 3 days and 4, 8, and 11 months post-injection using antibodies AT8 and MC1, which reveal early phosphorylation and aberrant conformation of tau, respectively, HT7, anti-synaptophysin, and the Gallyas silver staining method. Human tau oligomers and tau fibrils exhibited some similarities and some differences in their ability to seed and propagate tau-related changes. Both human tau fibrils and tau oligomers rapidly propagated from the mEC anterogradely into the hippocampus and various parts of the neocortex. However, using a human tau-specific HT7 antibody, 3 days post-injection we found inoculated human tau oligomers in the red nucleus, primary motor, and primary somatosensory cortex, a finding not seen in animals inoculated with human tau fibrils. In animals inoculated with human tau fibrils, 3 days post-injection the HT7 antibody showed fibrils in the pontine reticular nucleus, a finding explained only by uptake of human tau fibrils by incoming presynaptic fibers to the mEC and retrograde transport of inoculated human tau fibrils to the brainstem. Rats inoculated with human tau fibrils showed as early as 4 months after inoculation a spread of phosphorylated tau protein at the AT8 epitopes throughout the brain, dramatically faster propagation of neurofibrillary changes than with human tau oligomers. The overall severity of tau protein changes 4, 8, and 11 months after inoculation of human tau oligomers and tau fibrils correlated well with spatial working memory and cognition impairments, as measured by the T-maze spontaneous alternation, novel object recognition, and object location tests. We concluded that this non-trangenic rat model of tauopathy, especially when using human tau fibrils, demonstrates rapidly developing pathologic alterations in neurons, synapses, and identifiable pathways together with cognitive and behavioral changes, through the anterograde and retrograde spreading of neurofibrillary degeneration. Therefore, it represents a promising model for future experimental studies of primary and secondary tauopathies, especially AD. Sakrij dio sažetka
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaBiomedicines
Brojčani podacivol. 11, br. 4, 1004
e-ISSN2227-9059
DOIhttps://doi.org/10.3390/biomedicines11041004
URN:NBNurn:nbn:hr:105:475072
Datum objave publikacije2023-03-24
URL dokumentahttps://www.mdpi.com/2227-9059/11/4/1004
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2023-10-27 08:42:11
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