engleski

A new platform for characterization of the rat model of sporadic Alzheimer's disease

Introduction: Croatian scientist developed a rat model of sporadic Alzheimer’s disease (sAD) produced by intraventricular (icv) injection of streptozotocin (STZ), agent selectively toxic to particular brain cells. STZ-icv treated rats develop behavioral and neurochemical changes that resemble those found in sAD patients, and have been neurochemically characterized also by other scientists. However, in order to make a solid base for testing of possible novel drug therapies for sAD patients, this model needs comprehensive cytopathological characterization for its validation. This will be accomplished by collaborative research funded by Unity Through Knowledge Fund (UKF). UKF project aims to develop new installed capacity for research into sAD in Croatia, also to develop clear and tangible evidence of a functioning collaboration between home institutions of Croatian scientists living in Croatia and abroad, and finally to establish a new line of research to further characterize rat model of sporadic AD developed in Croatia. Methods: The project will employ a battery of light- and electron microscopic cytopathological methods to reveal amyloid-containing, senile plaque-like and neurofibrillary tangle-like lesions, as well as neuronal loss in order to test the hypothesis that the STZ-treated rats exhibit progressive AD-like pathology as time after injection increases. Cholinergic transmission in the hippocampus will be assed as well, at the level of receptor expression and enzyme activity. In full compliance with the UKF guidelines, this project is also designed to support basic and applied scientific research to create new knowledge and to directly and indirectly strengthen the Croatian biomedical infrastructure and economy. Results: The comprehensive battery of cytopathological methods and biochemical analyses of cholinergic neurotransmission in the STZ-icv rat model will provide data for correlation with the behavioral deficits on a dose-and time- dependent basis. This will further enable opportunity to characterize, compare and contrast AD-like lesions in the Croatian rat sAD model with actual patients with AD. The results of this research will provide a solid basis for future substantial international funding opportunities, and will also serve as a catalytic or “seeding” element to continue and expand the development of the biotechnology industry relevant to AD in Croatia. Conclusion: The results of this UKF funded research will substantially contribute to understanding sAD pathophysiology and in the long term enable exploration of novel, effective and targeted treatments for this major societal problem, leading to benefit of AD patients and society. Acknowledgement:Supported by Unity Through Knowledge Fund. Additionally supported by MZOS and DAAD.

streptozotocin; cytopathology; amyloid beta; NFT

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