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Projekt HRZZ: GALAD

THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN EXPERIMENTAL ALZHEIMER’S DISEASE
(GALAD)

HRZZ Research Project

Project leader (PI): Melita Šalković-Petrišić

Host institution: University of Zagreb School of Medicine, Zagreb, Croatia

Project duration: 36 months (15.09.2015. – 15.09.2018.)

Project funding: 750 000 HRK

PROJECT TEAM MEMBERS

Prof.dr.sc. Melita Šalković-Petrišić, M.D. (Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia)

Project team:

Dr.sc. Ana Knezović, dipl.ing.biol. (Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia)

Dr.sc. Jelena Osmanović-Barilar, M.D. (Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia)

Andrija Lončar, M.D. (Department of Neurology, General Hospital Karlovac, Karlovac, Croatia)

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) Ana KnezoviC, Jelena Osmanovic BarilaR, Ana Babic, Robert Bagaric, Vladimir Farkas, Peter Riederer, Melita Salkovic-Petrisic. Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

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) The effect of oral galactose on glucose homeostasis and memory in a transgenic mice model of familial Alzheimer’s disease Ana Babić1 , Jelena Osmanović Barilar1 , Ana Knezović1 , Robert Bagarić2 , Vladimir Farkaš2 , Peter Riederer3,4, Melita Šalković-Petrišić
2) Therapeutic galactose effect on metabolic dysfunction and cognition in sporadic rat model of Alzheimer’s disease Ana Knezovic1 , Jelena Osmanovic Barilar1 , Ana Babic1 , Robert Bagaric2 , Vladimir Farkas2 , Peter Riederer3,4, Melita Salkovic-Petrisic
3) 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 J. Osmanovic-Barilar1 , A. Knezovic1 , A. Babic1 , P. Riederer2,3 , M. Salkovic-Petrisic1
4) Babic A. COGNITIVE AND METABOLIC EFFECTS OF ORAL GALACTOSE IN STREPTOZOTOCIN-INDUCED RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE

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 "EFFECT OF ACUTE GALACTOSE ADMINISTRATION ON OXIDATIVE STRESS AND METABOLISM IN BRAIN STEM OF RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE"
7) Rektorova nagrada: Jan Holomak (student medicina) "BIOCHEMICAL CHANGES IN DORSAL MOTOR NUCLEUS OF VAGUS IN RAT MODEL OF SPORADIC ALZHEIMER'S DISEASE"

15.09.2016. – 14.09.2017.

Abstracts:

1) Ana Babić, Jelena Osmanović Barilar, Ana Knezović, Robert Bagarić, Vladimir Farkaš , Peter Riederer, Melita Šalković-Petrišić. ORAL GALACTOSE TREATMENT IMPROVES METABOLIC CHANGES IN A RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE; The13th International Conference on Alzheimers & Parkinsons disease, March 29 - April 2, 2017, Vienna, Austria
2) Jelena Osmanovic-Barilar, Ana Knezovic, Peter Riederer, Werner Reutter, Melita Salkovic-Petrisic. IMPROVED COGNITION IN STREPTOZOTOCIN-RAT MODEL OF SPORADIC ALZHEIMER DISEASE AFTER ORAL GALACTOSE TREATMENT
3) A. Babić, THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN TRANSGENIC MICE MODEL OF ALZHEIMER’S DISEASE; PhD Day, Unuversity of Zagreb School of Medicine, May 26, 2017, Zagreb, Croatia
4) J. Holmak, J. Osmanović Barilar, A. Babić, a. Knezovic, P. Riederer, M. Salkovic-Petrisic, ENVIRONMENTAL AND METABOLIC TERAPEUTIC STRATEGIES IMPROVE ANXIENTYLIKE BEHAVIOUR IN A RAT MODEL OF SPORADIC ALZHEIMERS DISEASE; Congress of the Worls Association of stress and Anxiety-related Disorders (WASAD), September 14-16, 2017, Wuzburg, Germany

15.09.2015. – 15.09.2016.

Abstracts:

1) ANNOUNCEMENT OF HRZZ PROJECT ON THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN EXPERIMENTAL ALZHEIMER’S DISEASE. Salkovic-Petrisic, Knezovic, Osmanovic Barilar, Reutter W. 8th Croatian Congress of Pharmacology wuth international participation, September 15-18, 2016, Split, Croatia
2) FACTORS CONTRIBUTING TO THERAPEUTIC POTENTIAL OF ORAL GALACTOSE IN A RAT MODEL OF SPORADIC ALZHEIMERS DISEASE Melita Salkovic-Petrisic, A. Knezovic, J. Osmanovic Barilar, W. Reutter. 2nd International Meeting of the Milan Centar for Neuroscience: Prediction and pervention of dementia: New Hope, July 6-8, 2016, Milan, Italy
3) Information about the project in official journal of School of Medicine (mef.hr, december 2015, page 98)