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Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice.
J Alzheimers Dis. 2010; 19(2):691-704.JA

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.

Authors+Show Affiliations

Clinic of Anesthesiology, University of Heidelberg Medical School, Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20110613

Citation

Plaschke, Konstanze, et al. "Insulin-resistant Brain State After Intracerebroventricular Streptozotocin Injection Exacerbates Alzheimer-like Changes in Tg2576 AbetaPP-overexpressing Mice." Journal of Alzheimer's Disease : JAD, vol. 19, no. 2, 2010, pp. 691-704.
Plaschke K, Kopitz J, Siegelin M, et al. Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. J Alzheimers Dis. 2010;19(2):691-704.
Plaschke, K., Kopitz, J., Siegelin, M., Schliebs, R., Salkovic-Petrisic, M., Riederer, P., & Hoyer, S. (2010). Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. Journal of Alzheimer's Disease : JAD, 19(2), 691-704. https://doi.org/10.3233/JAD-2010-1270
Plaschke K, et al. Insulin-resistant Brain State After Intracerebroventricular Streptozotocin Injection Exacerbates Alzheimer-like Changes in Tg2576 AbetaPP-overexpressing Mice. J Alzheimers Dis. 2010;19(2):691-704. PubMed PMID: 20110613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. AU - Plaschke,Konstanze, AU - Kopitz,Juergen, AU - Siegelin,Markus, AU - Schliebs,Reinhard, AU - Salkovic-Petrisic,Melita, AU - Riederer,Peter, AU - Hoyer,Siegfried, PY - 2010/1/30/entrez PY - 2010/1/30/pubmed PY - 2010/4/7/medline SP - 691 EP - 704 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 19 IS - 2 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20110613/Insulin_resistant_brain_state_after_intracerebroventricular_streptozotocin_injection_exacerbates_Alzheimer_like_changes_in_Tg2576_AbetaPP_overexpressing_mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-1270 DB - PRIME DP - Unbound Medicine ER -