Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat.

ABSTRACT

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.