Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat.
Streptozotocin is well known inducer of experimental diabetes mellitus when injected peripherally. However, when administered intracerebroventricular, streptozotocin showed a whole spectrum of specific biochemical and behavioural alterations with regard to cognitive functions, feeding, nociception, brain glucose metabolism, neurotransmission and oxidative stress, without producing arterial hyperglycaemia, similarly to Alzheimer's disease. In order to reveal the mechanism of action of neurodegeneration in streptozotocin rat model we investigated the expression of several genes involved in inflammation, oxidative stress, growth- and transcription-factors in the cortex, striatum and cerebellum, using real-time quantitative RT-PCR. Genes such as GDNF, BDNF and integrin-alpha-M were up-regulated, while immediate-early-gene-transcription-factor NGF-IB and metallothionein-1/2 were down-regulated in the cortex of streptozotocin-treated rats. Conversely, NGF-IB, GDNF and BDNF mRNA expression did not alter in the striatum and cerebellum. However, integrin alpha-M and metallothionein-1/2 expressions decreased significantly in the striatum and increased in the cerebellum. These gene changes may provide an insight into the cascade of physiological abnormalities following the inhibition of neuronal insulin signal transduction. Additionally, similarities to neuronal cell death in sporadic Alzheimer's disease may become apparent.
Grünblatt
Edna
E
Institute of Clinical Neurochemistry, National Parkinson Foundation Centre of Excellence Laboratories, Bayerische Julius-Maximilians- University of Würzburg, D-97080 Würzburg, Germany. edna.gruenblatt@mail.uni-wuerzburg.de
Koutsilieri
Eleni
E
Hoyer
Siegfried
S
Riederer
Peter
P
D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007276:Injections, Intraventricular; D007328:Insulin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D017931:DNA Primers; D007328:Insulin; D009419:Nerve Tissue Proteins; D013311:Streptozocin; D012313:RNA; D011972:Receptor, Insulin