TY  - JOUR
A1  - Bartl, Jasmin
A1  - Scholz, Claus-Jürgen
A1  - Hinterberger, Margareta
A1  - Jungwirth, Susanne
A1  - Wichart, Ildiko
A1  - Rainer, Michael K.
A1  - Kneitz, Susanne
A1  - Danielczyk, Walter
A1  - Tragl, Karl H.
A1  - Fischer, Peter
A1  - Riederer, Peter
A1  - Grünblatt, Edna
T1  - Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene
JF  - BMC Medical Genetics
N2  - Background

Insulin-degrading enzyme (IDE) is the ubiquitously expressed enzyme responsible for insulin and amyloid beta (Aβ) degradation. IDE gene is located on chromosome region 10q23-q25 and exhibits a well-replicated peak of linkage with Type 2 diabetes mellitus (T2DM). Several genetic association studies examined IDE gene as a susceptibility gene for Alzheimer's disease (AD), however with controversial results.

Methods

We examined associations of three IDE polymorphisms (IDE2, rs4646953; IDE7, rs2251101 and IDE9, rs1887922) with AD, Aβ42 plasma level and T2DM risk in the longitudinal Vienna Transdanube Aging (VITA) study cohort.

Results

The upstream polymorphism IDE2 was found to influence AD risk and to trigger the Aβ42 plasma level, whereas the downstream polymorphism IDE7 modified the T2DM risk; no associations were found for the intronic variant IDE9.

Conclusions

Based on our SNP and haplotype results, we delineate the model that IDE promoter and 3' untranslated region/downstream variation may have different effects on IDE expression, presumably a relevant endophenotype with disorder-specific effects on AD and T2DM susceptibility.
KW  - Insulin Degrading Enzyme
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137744
VL  - 12
IS  - 151
ER  - 
TY  - JOUR
A1  - Grünblatt, Edna
A1  - Bartl, Jasmin
A1  - Iuhos, Diana-Iulia
A1  - Knezovic, Ana
A1  - Trkulja, Vladimir
A1  - Riederer, Peter
A1  - Walitza, Susanne
A1  - Salkovic-Petrisic, Melita
T1  - Characterization of cognitive deficits in spontaneously hypertensive rats, accompanied by brain insulin receptor dysfunction
JF  - Journal of Molecular Psychiatry
N2  - Background
The spontaneously hypertensive rat (SHR) has been used to model changes in the central nervous system associated with cognitive-related disorders. Recent human and animal studies indicate a possible relationship between cognitive deficits, insulin resistance and hypertension. We aimed to investigate whether cognitively impaired SHRs develop central and/or peripheral insulin resistance and how their cognitive performance is influenced by the animal’s sex and age as well as strains used for comparison (Wistar and Wistar-Kyoto/WKY).

Methods
Three and seven-month-old SHR, Wistar, and WKY rats were studied for their cognitive performance using Morris Water Maze (MWM) and Passive Avoidance tests (PAT). Plasma glucose and insulin were obtained after oral glucose tolerance tests. Cerebral cortex, hippocampus, and striatum status of insulin-receptor (IR) β-subunit and glycogen synthase kinase-3β (GSK3β) and their phosphorylated forms were obtained via ELISA.

Results
SHRs performed poorly in MWM and PAT in comparison to both control strains but more pronouncedly compared to WKY. Females performed poorer than males and 7-month-old SHRs had poorer MWM performance than 3-month-old ones. Although plasma glucose levels remained unchanged, plasma insulin levels were significantly increased in the glucose tolerance test in 7-month-old SHRs. SHRs demonstrated reduced expression and increased activity of IRβ-subunit in cerebral cortex, hippocampus, and striatum with different regional changes in phospho/total GSK3β ratio, as compared to WKYs.

Conclusion
Results indicate that cognitive deficits in SHRs are accompanied by both central and peripheral insulin dysfunction, thus allowing for the speculation that SHRs might additionally be considered as a model of insulin resistance-induced type of dementia.
KW  - spontaneously hypertensive rat
KW  - age
KW  - control strain
KW  - gender
KW  - glycogen synthase kinase-3β
KW  - insulin resistance
KW  - learning and memory
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149593
VL  - 3
IS  - 6
ER  -