Insulin-Resistant Brain State after Intracerebroventricular Streptozotocin Injection Exacerbates Alzheimer-like Changes in Tg2576 AβPP-Overexpressing Mice

Plaschke, Konstanze; Kopitz, Juergen; Siegelin, Markus; Schliebs, Reinhard; Salkovic-Petrisic, Melita; Riederer, Peter; Hoyer, Siegfried

doi:10.3233/jad-2010-1270

Cited by 120Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Insulin-Resistant Brain State after Intracerebroventricular Streptozotocin Injection Exacerbates Alzheimer-like Changes in Tg2576 AβPP-Overexpressing Mice

Plaschke, Konstanze, Kopitz, Juergen, Siegelin, Markus, Schliebs, Reinhard, Salkovic-Petrisic, Melita, Riederer, Peter, Hoyer, Siegfried·2010·Journal of Alzheimer s Disease

DOI 10.3233/jad-2010-1270

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Abstract

For studying rare hereditary Alzheimer's disease (AD), transgenic (Tg) animal models overexpressing amyloid-beta protein precursor (AbetaPP) followed by increased amyloid-beta (Abeta) 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) alpha/beta content, and the formation of AD-like morphological hallmarks Abeta and tau protein in AbetaPP 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 Abeta40/42 fragments, total and phosphorylated tau protein, and GSK-3alpha/beta were determined by ELISA. Cerebral (immuno)histological analyses were performed. In Tg mice, STZ treatment increased mortality, reduced spatial cognition, and increased cerebral aggregated Abeta fragments, total tau protein, and congophilic amyloid deposits. These changes were associated with decreased GSK-3alpha/beta ratio (phosphorylated/total). A linear negative correlation was detected between Abeta42 and cognition, and between GSK-3alpha/beta ratio and aggregated Abeta40+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-3alpha/beta pathway in AbetaPP-overexpressing mice.

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Experimentally-induced diabetes causes accelerated cognitive failure in AD mouse models.
“Experimentally-induced diabetes moreover causes accelerated cognitive failure in AD mouse models (Cao et al., 2007; Ho et al., 2004; Plaschke et al., 2010; Wang et al., 2010).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Plaschke et al., 2010

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Background
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Self-citation
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Self-citation
Astrocyte dysfunction alters GABAergic communication and ammonia metabolism in the streptozotocin-induced sporadic Alzheimer's disease model
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Background
Centella asiatica improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice
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Insulin signaling disruption exacerbates memory impairment and seizure susceptibility in an epilepsy model with Alzheimer’s disease-like pathology
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“…injections at a dose of 1.25 mg/kg exacerbate spatial memory deficits in the Morris Water Maze (MWM) test in Tg2576 AβPP-overexpressing mice (Plaschke et al. 2010), a transgenic line that overexpresses the human AβPP with the Swedish mutation (APP695swe, K670N/M671L) (Kawarabayashi et al.…”
Influential
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Authors: Plaschke, K., Kopitz, J., Siegelin, M., Schliebs, R., Salkovic-Petrisic, M., Riederer, P., & Hoyer, S.
Affiliations: Heidelberg University (DE)
Leipzig University (DE)
Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia
Universitätsklinikum Würzburg (DE)
Corresponding author: Plaschke, Konstanze
ORCID: Plaschke, Konstanze
Siegelin, Markus
Riederer, Peter
Hoyer, Siegfried
Venue: Journal of Alzheimer s Disease
Publisher: SAGE Publications
Published: 2010-01-07
Volume: 19
Issue: 2
Pages: 691-704
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2010-1270
OpenAlex: W1802455527
Cited by: 118
References: 0
Citations by year: 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 3 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 13 · 2012: 10
FWCI: 8.02
Type: journal article
Language: en
Open access: closed
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: insulin resistance, brain
MeSH terms: Glycogen Synthase Kinase 3 beta, Age Factors, Alzheimer Disease, Animals, Avoidance Learning, Brain, Diabetes Mellitus, Experimental, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Injections, Intraventricular, Insulin Resistance, Memory Disorders, Mice, Transgenic, Mutation, Psychomotor Performance, Reaction Time, Streptozocin, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Apoptosis, Maze Learning, In Situ Nick-End Labeling, Glycogen Synthase Kinase 3, Mice, Plaque, Amyloid

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Insulin-Resistant Brain State after Intracerebroventricular Streptozotocin Injection Exacerbates Alzheimer-like Changes in Tg2576 AβPP-Overexpressing Mice

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