Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Knezović, Ana and Osmanović Barilar, Jelena and Babić, Ana and Bagarić, Robert and Farkaš, Vladimir and Riederer, Peter and Šalković-Petrišić, Melita (2018) Glucagon-like peptide-1 mediates effects of oral galactose in streptozotocin-induced rat model of sporadic Alzheimer’s disease. Neuropharmacology, 135. pp. 48-62. ISSN 0028-3908

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Abstract

Insulin resistance and metabolic dysfunction in the brain are considered to be the pathophysiological core of sporadic Alzheimer's disease (sAD). In line with that fact, nutrients that could have therapeutic effects at this level have been investigated as possible targets in AD therapy. Galactose, an epimer of glucose, may serve as an alternative source of energy, and given orally may stimulate secretion of the incretin hormone glucagon-like peptide-1 (GLP-1). Our preliminary research indicated that oral galactose might prevent development of memory impairment in a rat model of sAD generated by intracerebroventricular administration of streptozotocin (STZ-icv). Here, we explored whether chronic oral galactose treatment could have beneficial effects on cognitive deficits already manifested at the time of initiation of galactose treatment in adult STZ-icv rats (treatment initiated 1 month after STZ-icv injection). The results clearly show that a 2-month exposure to oral galactose (200 mg/kg/day administered in a drink ad libitum) normalises impaired learning and memory functions. Memory improvement was accompanied by an improvement in brain glucose hypometabolism measured by 18fluorodeoxyglucose-positron emission tomography neuroimaging and by increments in active GLP-1 plasma levels as well as by an increased expression of GLP-1 receptors in the hippocampus and hypothalamus. Our findings provide strong evidence of beneficial effects of oral galactose treatment in the STZ-icv rat model of sAD and present possible underlying mechanisms including both direct effects of galactose within the brain and indirect GLP-1-induced neuroprotective effects that might open a new, dietary-based strategy in sAD treatment.

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