Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AβPP-overexpressing mice
For studying rare hereditary Alzheimer's disease (AD), transgenic (Tg) animal models overexpressing amyloid-β protein precursor (AβPP) followed by increased amyloid-β (Aβ) formation are used. In contrast, sporadic AD has been proposed to start with an insulin-resistant brain state (IRBS). We in...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
7 January 2010
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| In: |
Journal of Alzheimer's disease
Year: 2010, Volume: 19, Issue: 2, Pages: 691-704 |
| ISSN: | 1875-8908 |
| DOI: | 10.3233/JAD-2010-1270 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3233/JAD-2010-1270 Verlag, lizenzpflichtig, Volltext: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad01270 
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| Author Notes: | Konstanze Plaschke, Juergen Kopitz, Markus Siegelin, Reinhard Schliebs, Melita Salkovic-Petrisic, Peter Riederer, Siegfried Hoyer |
| Summary: | For studying rare hereditary Alzheimer's disease (AD), transgenic (Tg) animal models overexpressing amyloid-β protein precursor (AβPP) followed by increased amyloid-β (Aβ) formation are used. In contrast, sporadic AD has been proposed to start with an insulin-resistant brain state (IRBS). We investigated the effect of IRBS induced by intracerebroventricularly (icv) administered streptozotocin (STZ) on behavior, glycogen synthase kinase-3 (GSK)α/β content, and the formation of AD-like morphological hallmarks Aβ and tau protein in AβPP Tg2576 mice. Nine-month-old Tg mice were investigated 6 months after a single icv injection of STZ or placebo. Spatial cognition was analyzed using the Morris water maze test. Soluble and aggregated Aβ40/42 fragments, total and phosphorylated tau protein, and GSK-3α/β were determined by ELISA. Cerebral (immuno)histological analyses were performed. In Tg mice, STZ treatment increased mortality, reduced spatial cognition, and increased cerebral aggregated Aβ fragments, total tau protein, and congophilic amyloid deposits. These changes were associated with decreased GSK-3α/β ratio (phosphorylated/total). A linear negative correlation was detected between Aβ42 and cognition, and between GSK-3α/β ratio and aggregated Aβ40+42. No marked necrotic and apoptotic changes were observed. In conclusion, IRBS may aggravate AD-like changes such as behavioral and increase the formation of pathomorphological AD hallmarks via GSK-3α/β pathway in AβPP-overexpressing mice. |
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| Item Description: | Gesehen am 04.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1875-8908 |
| DOI: | 10.3233/JAD-2010-1270 |