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Therapeutic effect of oral galactose treatment in rat model of sporadic Alzheimer's disease


Šalković-Petrišić, Melita; Knezović, Ana; Osmanović-Barilar, Jelena; Reutter, Werner
Therapeutic effect of oral galactose treatment in rat model of sporadic Alzheimer's disease // Alzheimer's Association International Conference (AAIC) 2014
Copenhagen, Danska, 2014. (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
Therapeutic effect of oral galactose treatment in rat model of sporadic Alzheimer's disease

Autori
Šalković-Petrišić, Melita ; Knezović, Ana ; Osmanović-Barilar, Jelena ; Reutter, Werner

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Alzheimer's Association International Conference (AAIC) 2014

Mjesto i datum
Copenhagen, Danska, 12-17.07.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Galactose; Alzheimer's disease; streptozotocin; cognition; insulin receptor

Sažetak
Background Sporadic Alzheimer's disease (sAD) is associated with insulin resistant brain state and decreased glucose metabolism in brain. In such a condition D-galactose might represent an alternative source of energy as it is transported into the brain cells by insulin-independent glucose transporter-3 where it is converted into glucose. Our recently published research showed that chronic oral galactose treatment improves cognitive deficits in intracerebroventricular streptozotocin-induced (STZ-icv) rat model of sAD. In the current research we have compared the effects of chronic oral and parenteral galactose treatment on cognitive functions and insulin receptor (IR) expression in the hippocampus (HPC) of STZ-icv rat model. Methods Adult male Wistar rats were injected bilaterally icv with STZ (1 mg/kg) or vehicle (controls) and immediately subjected to one month daily oral (200 mg/kg in a drinking water, 20 mL/rat/day) or parenteral (100 mg/kg, intraperitoneal injection) galactose treatment. Cognitive deficits were measured by Morris Water Maze (MWM) and Passive Avoidance (PA) tests before sacrifice. Hippocampal IR protein expression was measured by SDS-PAGE electrophoresis, followed by Western blot analysis. Data were analysed by Kruskal-Wallis and Mann-Whitney U test (p<0.05). Results In comparison to the untreated control, STZ-icv rats demonstrated cognitive deficits (-88% PA ; +143 MWM, p<0.05) which have been normalized by chronic galactose oral (+9%PA ; -34% MWM, p<0.05) but not parenteral (-71% PA ; +31% MWM, p<0.05) treatment, respectively. Control rats treated by parenteral galactose also demonstrated cognitive deficits (-73% PA ; +46 MWM, p<0.05). Parenteral galactose treatment significantly increased hippocampal IR expression in control rats (+68%) as well as in STZ-icv rats regardless the route of administration (+28% oral ; +46% parenteral route), in comparison to the untreated control rats. Conclusion Chronic oral daily galactose treatment normalizes cognitive deficits developed in STZ-icv rat model of sAD while parenteral galactose treatment is not worsening them but is completely ineffective in this respect. These administration route-dependent differences in effects on cognition seem not to be mediated by galactose effect on hippocampal IR expression. Chronic exposure to oral galactose as nutrient might be a promising novel strategy in the treatment of sAD. Supported by MZOS (108-1080003-0020).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
108-1080003-0020 - Mozak, eksperimentalni i cerebralni dijabetes i kognitivni i drugi poremećaji (Melita Šalković-Petrišić, )

Ustanove
Medicinski fakultet, Zagreb