engleski

Early changes of cholinergic receptors in hippocampus and parietotemporal cortex of the rat model of sporadic Alzhimer's disease

Introduction Numerous studies have shown alterations of cholinergic receptors in sporadic Alzheimer’s disease (sAD). In spite of some inconsistency in results, reduced expression of muscarinic M1 and M4, and nicotinic α7 (α7) receptor, respectively, has been frequently found in the brain of sAD patients post mortally. However, such reductions may not occur until the advanced stage of the disease. Early, preclinical changes are difficult to be tracked in humans but can be followed in animal AD models. Streptozotocin (STZ)- intracerebroventricularly (icv) treated rats, have been recently proposed as an experimental sAD model, suitable for determining brain neurochemical changes appearing immediately after the STZ-induced brain damage. Methods Adult Male Wistar rats were injected with three doses of STZ (0.3-3 mg/kg) or vehicle (controls) bilaterally into the lateral ventricles. Animals were sacrificed one week after the STZ-icv treatment. Protein expression of M1, M4 and α7 receptors was measured in hippocampus (HPC) and parietotemporal cortex (PTC) by SDS-PAGE electrophoresis followed by Western Blot. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results In comparison to controls, the expression of muscarinic M4 receptor was found significantly increased (+38.5%) in HPC with the highest STZ-icv dose. Protein expression of muscarinic M1 receptor demonstrated a clear tendency to decrease in both regions following the highest STZ-icv dose only (- 25.35% HPC ; -18.27% PTC), which due to a high variability did not reach the statistical significance. No significant changes in nicotinic α7 receptor expression were found in both regions. Conclusion Muscarinic M4 receptors seem to be more susceptible than M1 and nicotinic α7 receptors and demonstrate an acute response to the STZ-icv administration in the early post-treatment phase. Longer follow up studies in a progress will show the onset and development of cholinergic receptor pathology and their correlation with cognitive deficits in STZ- icv rat sAD model. Acknowledgement Supported by UKF, MZOS (108-1080003-0020).

muscarinic and nicotinic cholinergic receptors; streptozotocin; Alzheimer's disease

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