Characterization of a Novel hAPP/Tau Mouse Model of Alzheimer's Disease: Exploring the Impact of Zinc Supplementation
Başlık:
Characterization of a Novel hAPP/Tau Mouse Model of Alzheimer's Disease: Exploring the Impact of Zinc Supplementation
Yazar:
Lippi, Stephen Lawrence Patrick, author. (orcid)0000-0002-2306-9022
ISBN:
9780438115026
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (112 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Jane M. Flinn Committee members: Geraldine Grant; Tyler Shaw.
Özet:
Mice bearing both amyloid and tau pathology are critical for modeling and studying Alzheimer's disease (AD). The brains of those suffering from AD have both of these pathological hallmarks; thus, it is crucial that mice made to model this disease have both. Through use of these double transgenic mice, researchers can study how both interact and lead to disturbances in the brain and behavior. In this study, we characterize offspring from the cross of the J20 (hAPP) and rTg4510 (tau) mouse strains, behaviorally at both three and a half and seven months and biochemically at eight months, on and off zinc (Zn) water. The double Tg mice (hAPP/Tau) were compared to single tau mice containing the P301L tau mutation under the CaMKIIa promoter, mice solely expressing the promoter with no tau mutation, and wildtype (WT) mice with no mutations. hAPP/Tau mice spent less time in the center of the open field, indicative of increased anxiety and made more head dips and spent more time in the open arms of the elevated zero maze (EZM) compared to WT mice (p < .001). This conjunction of decreased time in the OF center and increased time in the open arms of the EZM is thought to represent behavioral disinhibition. hAPP/Tau mice showed deficits in spatial memory as assessed by the Barnes Maze; hAPP/Tau mice spent significantly less time in the target quadrant during the probe trial compared to WT mice and worsened with age (p < .01). hAPP/Tau mice spent longer amounts of time swimming at seven months compared to three and a half months in the forced swim (FS) test (p < .05).
In the brain, hAPP/Tau mice had significantly less free zinc compared to WT mice in both the dentate gyrus and the CA3 of the hippocampus ( p < .001) as detected by Zinpyr-1 fluorescence. hAPP/Tau mice and single tau mice had significantly greater inflammation, seen through GFAP immunoblotting, than CaMKIIa promoter mice (p < .05). Increased Thioflavin-S fluorescence and increased plaques were noted in the hippocampus of hAPP/Tau mice compared to single tau mice. Animals given Zn water displayed increased tangle pathology, as seen by greater Thioflavin-S fluorescence in the hippocampus and hAPP/Tau mice had a greater amount of tangles than single tau mice on average. hAPP/Tau mice showed severe behavioral deficits at the first testing period; this may have masked any effects Zn supplementation may have been playing on behavior. The hAPP/Tau mouse described here displays pathology reminiscent of the human AD condition and serves as a new model for researchers to assess how both amyloid and tau pathology can together impact the brain and behavior.
Notlar:
School code: 0883
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(692085.1) | 692085-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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