Background: Type 1 diabetes (T1D) is an organ-specific autoimmune disease that results from T cell-mediated destruction of insulin-producing pancreatic beta cells in genetically predisposed individuals. Numerous studies have shown that the inflammation induced by hyperglycemia is the main mechanism of the pathogenesis of diabetic neuropathy. The relationship between inflammation and diabetic neuropathy progression included the processes and complex molecular networks. There is compelling evidence that the innate immune system plays a key role in early mechanisms triggering diabetes. Toll like receptors (TLRs) are key molecules recognizing foreign and endogenous danger signals, activating and regulating innate immunity and inflammation, and finally inducing adaptive immunity. TLRs have been shown to play essential roles in infections, inflammatory diseases and cancer. A number of studies demonstrated that TLRs mediated innate immune responses could contribute to the induction of diabetes. Abundant evidence also suggests that TLRs are important players in neurodegenerative diseases, which involve many inflammatory components. Although many studies have shown that these genes are induced in diabetes, it is not clear whether these gene are involved in the development of diabetes. The role of inflammation in neurological diseases has been recently confirmed. Methods: In this study the time course expression of the TLR2 and TLR4 genes in hippocampal brain tissue of diabetic male Wistar rats were studied. Hyperglycemia was induced in male wistar rats with intraperitoneal (I.P.) injection of Streptozotocin. In different time points (4, 6, 8 and 20 weeks) post diabetes type 1 induction, rats were euthanized and hippocampal brain tissues was removed for further analysis. RNA was extracted from hippocampal brain tissues samples followed by cDNA synthesization using oligo-dT primers. Exon specific TLR2 and TLR4 primers were used to amplify rat TLR2 and TLR4 cDNA. After performing semiquantitative RT-PCR, the expression level of TLR4 mRNA was quantified by real time quatitative PCR (qPCR). Results: Up-regulation of TLR2 and TLR4 transcripts during the time course after diabetes induction as compared to the control group was shown. Conclusion: Our results demonstrate that the expression of TLRs may play a decisive role in the pathogenesis and expansion of diabetes. It is possible that the expression of TLRs can eventually lead to neurodegenerative disease such as Alzheimer. Therefore, studies on the precise role of TLRs in neurodegenerative disease may yield potential molecular targets for developing therapeutics for control and prevention of diabetic neurodegenerative disorders.

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