PMID- 20110613
OWN - NLM
STAT- MEDLINE
DCOM- 20100406
LR  - 20161125
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 19
IP  - 2
DP  - 2010
TI  - Insulin-resistant brain state after intracerebroventricular streptozotocin 
      injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing 
      mice.
PG  - 691-704
LID - 10.3233/JAD-2010-1270 [doi]
AB  - 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.
FAU - Plaschke, Konstanze
AU  - Plaschke K
AD  - Clinic of Anesthesiology, University of Heidelberg Medical School, Heidelberg, 
      Germany.
FAU - Kopitz, Juergen
AU  - Kopitz J
FAU - Siegelin, Markus
AU  - Siegelin M
FAU - Schliebs, Reinhard
AU  - Schliebs R
FAU - Salkovic-Petrisic, Melita
AU  - Salkovic-Petrisic M
FAU - Riederer, Peter
AU  - Riederer P
FAU - Hoyer, Siegfried
AU  - Hoyer S
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (tau Proteins)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Age Factors
MH  - Alzheimer Disease/complications/*genetics/mortality/*pathology
MH  - Amyloid beta-Peptides/metabolism
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Avoidance Learning/drug effects/physiology
MH  - Brain/drug effects/*metabolism
MH  - Diabetes Mellitus, Experimental/chemically 
      induced/complications/mortality/*pathology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - In Situ Nick-End Labeling/methods
MH  - Injections, Intraventricular/methods
MH  - Insulin Resistance
MH  - Maze Learning/drug effects/physiology
MH  - Memory Disorders/chemically induced
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation/genetics
MH  - Plaque, Amyloid/genetics/pathology
MH  - Psychomotor Performance/drug effects/physiology
MH  - Reaction Time/drug effects/genetics
MH  - Streptozocin/*toxicity
MH  - tau Proteins/metabolism
EDAT- 2010/01/30 06:00
MHDA- 2010/04/07 06:00
CRDT- 2010/01/30 06:00
PHST- 2010/01/30 06:00 [entrez]
PHST- 2010/01/30 06:00 [pubmed]
PHST- 2010/04/07 06:00 [medline]
AID - Q7752551841H7437 [pii]
AID - 10.3233/JAD-2010-1270 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2010;19(2):691-704. doi: 10.3233/JAD-2010-1270.