PMID- 17448147
OWN - NLM
STAT- MEDLINE
DCOM- 20070718
LR  - 20220409
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 101
IP  - 3
DP  - 2007 May
TI  - Brain insulin system dysfunction in streptozotocin intracerebroventricularly 
      treated rats generates hyperphosphorylated tau protein.
PG  - 757-70
AB  - The intracerebroventricular (icv) application of streptozotocin (STZ) in low 
      dosage was used in 3-month-old rats to explore brain insulin system dysfunction. 
      Three months following STZ icv treatment, the expression of insulin-1 and -2 mRNA 
      was significantly reduced to 11% in hippocampus and to 28% in frontoparietal 
      cerebral cortex, respectively. Insulin receptor (IR) mRNA expression decreased 
      significantly in frontoparietal cerebral cortex and hippocampus (16% and 33% of 
      control). At the protein/activity level, different abnormalities of protein 
      tyrosine kinase activity (increase in hippocampus), total IR beta-subunit 
      (decrease in hypothalamus) and phosphorylated IR tyrosine residues (increase) 
      became apparent. The STZ-induced disturbance in learning and memory capacities 
      was not abolished by icv application of glucose transport inhibitors known to 
      prevent STZ-induced diabetes mellitus. The discrepancy between reduced IR gene 
      expression and increase in both phosphorylated IR tyrosine residues/protein 
      tyrosine kinase activity may indicate imbalance between 
      phosphorylation/dephosphorylation of the IR beta-subunit causing its dysfunction. 
      These abnormalities may point to a complex brain insulin system dysfunction after 
      STZ icv application, which may lead to an increase in hyperphosphorylated 
      tau-protein concentration. Brain insulin system dysfunction is discussed as 
      possible pathological core in the generation of hyperphosphorylated tau protein 
      as a morphological marker of sporadic Alzheimer's disease.
FAU - Grunblatt, Edna
AU  - Grunblatt E
AD  - Clinical Neurochemistry and National Parkinson Foundation Centre of Excellence 
      Laboratory, Clinic for Psychiatry and Psychotherapy, Bayrische Julius-Maximilian 
      University of Wurzburg, Wurzburg, Germany. edna.gruenblatt@mail.uni-wuerzburg.de
FAU - Salkovic-Petrisic, Melita
AU  - Salkovic-Petrisic M
FAU - Osmanovic, Jelena
AU  - Osmanovic J
FAU - Riederer, Peter
AU  - Riederer P
FAU - Hoyer, Siegfried
AU  - Hoyer S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - 0 (tau Proteins)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Behavior, Animal
MH  - Brain Diseases/chemically induced/*metabolism/physiopathology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Injections, Intraventricular/methods
MH  - Insulin/*metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - Phosphorylation/drug effects
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Insulin/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Statistics, Nonparametric
MH  - Streptozocin
MH  - Time Factors
MH  - tau Proteins/*metabolism
EDAT- 2007/04/24 09:00
MHDA- 2007/07/19 09:00
CRDT- 2007/04/24 09:00
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/07/19 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
AID - JNC4368 [pii]
AID - 10.1111/j.1471-4159.2006.04368.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 May;101(3):757-70. doi: 10.1111/j.1471-4159.2006.04368.x.