TERAPIJSKI POTENCIJAL ORALNE GALAKTOZE U EKSPERIMENTALNOJ ALZHEIMEROVOJ BOLESTI

THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN EXPERIMENTAL ALZHEIMER'S DISEASE

This project aims to explore a novel therapeutic strategy in Alzheimer’s disease (AD), the most common form of dementia. Owing to growing evidence of brain insulin resistance (BIR) and cerebral metabolic dysfunction being the mediators of sporadic AD (sAD), restoring of brain insulin signalling and downstream defects has recently become a new target in AD treatment research. Unique contribution of this proposal is in characterization of the therapeutic potential of oral galactose in animal models which mimic sAD and familial AD. The former is generated by streptozotocin-intracerebroventricular application (STZ-icv rat) which induces BIR and eventually develops many of sAD-like features, and the latter is transgenic Tg2576 mice which eventually show some signs of BIR. Galactose is alternative source of energy; it enters the cell via insulin-independent glucose transporter GLUT3 and is metabolized to glucose. PI’s recent publication indicates that oral galactose prevents development of cognitive deficits in STZ-icv rat model. This research will explore if it can prevent them in Tg2576 mice and ameliorate already developed cognitive deficits in both Tg2576 mice and STZ-icv rats. Innovative aspect of the proposal is elucidation of oral galactose-mediated improvement in cerebral glucose uptake and stimulation of glucagone-like peptide-1 (GLP-1) secretion, and their correlation to cognitive improvement in both models. Morris Water Maze and Passive Avoidance tests, radio-tracing of brain glucose metabolism, Western blot analysis, Enzyme-Linked Immunosorbent Assays and immunohistochemistry will be used to detect effects of 2-month oral galactose treatment on memory loss, GLUT3/GLUT4 and insulin degrading enzyme levels, tau and amyloid-ß pathology in the brain, and galactose, insulin and GLP-1 levels in blood/cerebrospinal fluid. Project results will gain new knowledge and provide significant insights into a novel nutrient-related therapeutic strategy in AD treatment.