Mechanisms of nutrient-mediated effects of endogenous glucagon-like peptide -1 on cognitive and metabolic alterations in experimental models of neurodegenerative disorders
This project aims to continue the previous research on oral galactose treatment in experimental Alzheimer’s disease (AD) by in depth characterization of mechanisms of its therapeutic activity in experimental AD and Parkinson disease (PD). Common pathological features between these neurodegenerative disorders (ND) exist on multiple levels, of which cognitive impairment is in the focus of this proposal. Currently there is no cure for ND and no approved disease-modifying therapy. Based on new evidence on cerebral glucose hypometabolism and insulin resistant brain state (IRBS) as a pathophysiological core, drugs acting like or stimulating the action of the incretin glucagon-like peptide-1 (GLP-1) are becoming more and more investigated in AD clinical trials. Literature data on the correlation between PD, IRBS and diabetes is much more discrepant than those of AD, although GLP-1-related drugs are currently being tested in PD clinical trials as well. By combining GLP-1-related and nutrients-based trends in accomplishing desirable neuroprotective effects in ND treatment, this research will explore oral galactose (nutrient)-promoted activity of endogenous GLP-1 in non-transgenic rat models of toxin-induced sporadic AD (sAD) and PD. In contrast to the harmful effects of parenteral galactose, our ongoing research in the streptozotocin-induced rat model of sAD (STZ-icv model) has provided evidence that oral galactose (depending on the used test) ameliorates or normalizes previously developed cognitive impairment in the early stage of sAD pathology, possibly by normalizing reduced glucose metabolism in the brain and by increasing active GLP-1 blood levels. These novel findings have laid ground for this project.
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3.Babić Perhoč A, Homolak J, Knezović A, Osmanović Barilar J, Šalković-Petrišić , TIME RESPONSE OF ORAL GALACTOSE ON METABOLIC EFFECTS IN COGNITIVELY NORMAL RATS, 9th Croatian Congress of Pharmacology with International Participation, Zagreb, 25 − 28 September 2019
4.Homolak J, Babić Perhoč, Knezović A, Osmanović Barilar J, ŠalkovićPetrišić M, ACUTE ORAL GALACTOSE TREATMENT DECREASES OXIDATIVE STRESS IN RAT BRAIN AND PLASMA IN TIME-DEPENDENT MANNERS, 9th Croatian Congress of Pharmacology with International Participation, Zagreb, 25 − 28 September 2019
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6.Babić Perhoč A, Homolak J, Knezović A, Osmanović Barilar J, Šalković-Petrišić M, STRESS AND NEUROINFLAMMATION AS POSSIBLE MEDIATORS OF ACUTE COGNITIVE DYSFUNCTION IN A STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE, WASAD Congress: Stress, Anxiety and Mental Health, Würzburg, Germany, 3 – 5 October 2019
7.Homolak J, Babić Perhoč A, Knezović A, Osmanović Barilar J, Relja M, Riederer P, Šalković-Petrišić M, MECHANISM OF NUTRIENT-MEDIATED EFFECTS OF ENDOGENOUS GLUCAGON-LIKE PEPTIDE-1 ON COGNITIVE AND METABOLIC ALTERNATIONS IN EXPERIMENTAL MODELS OF NEURODEGENERATIVE DISORDERS, Science and Educational Challenges Facing Europe in the Next Decade, on the occasion of the 250th anniversary of the birth of Alexander von Humboldt (1769–1859) Humboldt College Zagreb, 10–11 October 2019
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