Projekt HRZZ: GALAD

Ana Babić, mag. pharm (Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia)
Prof.dr.sc. Peter Riederer (Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg)
Prof. dr. sc. Edna Grünblatt (Child and Adolescent Psychiatry Canton Zurich University of Zurich, Zurich, Swiss)

Project synopsis

Brain insulin resistance and cerebral metabolic dysfunction were found in sporadic Alzheimer’s disease (sAD). This project aims to explore a novel therapeutic strategy, oral galactose treatment (alternative source of energy) in sAD animal model (streptozotocin-intracerebroventricularly (STZ-icv) treated rat model) and familial AD model (transgenic Tg2576 mouse model). Previously it was found that galactose treatment has beneficial effects on prevention of cognitive deficit development in a STZ-icv model and this research will explore if it may prevent the appearance of cognitive deficits in Tg2576 mice and ameliorate already developed cognitive deficits in both Tg2576 mice and STZ-icv rats. This project aims also to elucidate oral galactose-mediated effects on glucose uptake and stimulation of glucagone-like peptide-1 (GLP-1) secretion, and their correlation to cognitive improvement in both models using cognitive tests, radio-tracing of brain glucose metabolism, and biochemical and histological analysis. Project results will gain new knowledge of metabolic aspects in AD pathophysiology and provide significant insights into a novel nutrient-related therapeutic strategy in AD treatment

Objectives

To explore and compare the effects of different doses of single oral and parenteral galactose administration on plasma and CSF levels of galactose, glucose, insulin and GLP-1, as possible mechanisms underlying previously reported opposite effects of oral and parenteral galactose on cognition.
To explore the therapeutic activity of chronic oral galactose treatment in sporadic AD (STZ-icv rat model) and familial (transgenic Tg2576 mice model) AD models.
To explore possible mechanisms underlying the neuroprotective potential of chronic oral galactose in experimental AD models, in particular those affecting cerebral glucose uptake and/or GLP-1-stimulation.

Results

15.09.2017. – 14.09.2018.

Research papers:

1) Knezovic A, Osmanovic Barilar J, Babic A, Bagaric R, Farkas V, Riederer P, Salkovic-Petrisic M. GLUCAGON-LIKE PEPTIDE-1 MEDIATES EFFECTS OF ORAL GALACTOSE IN STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE. Neuropharmacology 2018; 135: 48-62.

2) Salkovic-Petrisic M. ORAL GALACTOSE PROVIDES A DIFFERENT APPROACH TO INCRETIN-BASED THERAPY OF ALZHEIMER’S DISEASE. Journal of Neurology & Neuromedicine 2018; 3(4): 101-107

3) Babic Perhoc A, Osmanovic Barilar J, Knezovic A, Farkas V, Bagaric R, Svarc A, Grünblatt E, Riederer P, Salkovic-Petrisic M. COGNITIVE, BEHAVIORAL AND METABOLIC EFFECTS OF ORAL GALACTOSE TREATMENT IN THE TRANSGENIC TG2576 MICE. Neuropharmacology 2018; 148: 50-67.

Abstracts:

1) Babic A, Osmanovic Barilar J, Knezovic A, Bagaric R, Farkas V, Riederer P, Salkovic-Petrisic M. THE EFFECT OF ORAL GALACTOSE ON GLUCOSE HOMEOSTASIS AND MEMORY IN A TRANSGENIC MICE MODEL OF FAMILIAL ALZHEIMER’S DISEASE 11th FENS Forum of Neuroscience, July 7-11, 2018, Berlin, Germany (abstract accepted)

2) Knezovic A, Osmanovic Barilar J, Babic A, Bagaric R, Farkas V, Riederer P, Salkovic-Petrisic M. THERAPEUTIC GALACTOSE EFFECT ON METABOLIC DYSFUNCTION AND COGNITION IN SPORADIC RAT MODEL OF ALZHEIMER’S DISEASE. 18th World Congress of Basic and Clinical Pharmacology, July 1-6, 2018, Kyoto, Japan (abstract accepted)

3) Osmanovic Barilar J, Knezovic A, Babic A, Riederer P, Salkovic-Petrisic M. ACTIVATION OF GLUCAGON-LIKE PEPTIDE-1 RECEPTORS MIGHT BE A MECHANISM OF THE BENEFICIAL EFFECTS OF ORAL GALACTOSE IN STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE. 18th World Congress of Basic and Clinical Pharmacology, July 1-6, 2018, Kyoto, Japan (abstract accepted)

4) Babic A. COGNITIVE AND METABOLIC EFFECTS OF ORAL GALACTOSE IN STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE; PhD Day, University of Zagreb School of Medicine, May 25, 2018, Zagreb, Croatia (oral presentation)

5) Babic A. COGNITIVE AND METABOLIC EFFECTS OF ORAL GALACTOSE IN STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE; 22nd Young neuroscientists meeting, University of Ljubljana, June 22, 2018, Ljubljana, Slovenia (oral presentation)

6) Diplomski rad: Jan Homolak “Akutni učinak galaktoze na oksidativni stres i metabolizam u moždanom deblu štakorskog modela sporadične Alzheimerove bolest”

7) Rektorova nagrada: Jan Homolak (student medicine) “Biokemijske promjene dorzalne motorne jezgre vagusa u štakorskom modelu sporadične Alzheimerove bolesti”

15.09.2016. – 14.09.2017.

Abstracts:

1) Knezovic, J. Osmanovic Barilar, P. Riederer, W. Reutter, M. Salkovic-Petrisic, ORAL GALACTOSE TREATMENT IMPROVES METABOLIC CHANGES IN A RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE; The 13th International Conference on Alzheimer’s & Parkinson’s Disease, March 29 – April 2, 2017, Vienna, Austria

2) J. Osmanovic Barilar, A. Knezovic, P. Riederer, W. Reutter, M. Salkovic-Petrisic, IMPROVED COGNITION IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER DISEASE AFTER ORAL GALACTOSE TREATMENT; The 13th International Conference on Alzheimer’s & Parkinson’s Disease, March 29 – April 2, 2017, Vienna, Austria

3) A. Babić, THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN TRANSGENIC MICE MODEL OF ALZHEIMER’S DISEASE; PhD Day, University of Zagreb School of Medicine, May 26, 2017, Zagreb, Croatia

4) J. Homolak, J. Osmanovic Barilar, A. Babic, A. Knezovic, P. Riederer, M. Salkovic-Petrisic, ENVIRONMENTAL AND METABOLIC THERAPEUTIC STRATEGIES IMPROVE ANXIETYLIKE BEHAVIOUR IN A RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE; Congress of the Worls Association of stress and Anxiety-realted Disorders (WASAD), September 14-16, 2017, Würzburg, Germany

15.09.2015. – 15.09.2016.

Abstracts:

1) Salkovic-Petrisic M, Knezovic A, Osmanovic Barilar J, Reutter W. Announcement of HRZZ project on therapeutic potential of oral galactose in experimental Alzheimer’s disease. 8th Croatian Congress of Pharmacology with international participation, September 15-18, 2016, Split, Croatia

2) Salkovic-Petrisic M, Knezovic A, Osmanovic Barilar J, Reutter W. Factors contributing to therapeutic potential of oral galactose in a rat model of sporadic Alzheimer’s disease. 2nd International Meeting of the Milan Center for Neuroscience: Prediction and prevention of dementia: New Hope, July 6-8, 2016, Milan, Italy