Naslov
Oral galactose-induced cognitive improvement in streptozotocin-induced rat model of sporadic Alzheimer’s disease

Autori
Knezović, Ana ; Šalković-Petrišić, Melita ; Osmanović-Barilar, Jelena ; Hoyer, Siegfried ; Mosetter, Kurt ; Reutter, Werner

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

Skup
17th World Congress of Basic and Clinical Pharmacology

Mjesto i datum
Cape Town, Južnoafrička Republika, 13.07.2014. - 18.07.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
galactose; glucose; CSF; streptozotocin; Alzheimer; memory and learning

Sažetak
Background Literature data indicate that chronic parenteral administration of galactose causes cognitive deterioration in small rodents while the effect of chronic oral galactose treatment on cognition has never been explored. Since galactose is transported into the cells including neurons via insulin-independent glucose transporter and is then converted to glucose, galactose might represent an alternative source of energy in a condition of glucose hypometabolism and insulin resistance in the brain, both found in sporadic Alzheimer’s disease (sAD). We have investigated the effect of chronic oral galactose treatment on cognitive deficit in streptozotocin-induced (STZ-icv) rat model of sAD. Methods Adult male Wistar rats were given bilateral intracerebroventricular (icv) injection of STZ (1 mg/kg) or vehicle (controls). Oral galactose treatment (200 mg/kg) was initiated immediately after icv injections and continued for 1 month on daily basis until sacrifice. Cognitive deficits were measured by Morris Water Maze (MWM) and Passive Avoidance (PA) Test. In additional experiment single galactose dose (100 mg/kg) was given to intact rats orally or intraperitoneally while control rats had no treatment at all, and animals were sacrificed 15 minutes afterwards. Glucose and galactose concentration in the second experiment was measured spectrophotometrically in plasma and cerebrospinal fluid (CSF). Results In comparison to the untreated controls, STZ-icv rats exhibited significant cognitive deficits (-76% PA ; +138% MWM, p<0.05) 1 month after icv treatment, which have not been found in chronic oral galactose treated-STZ-icv rats (+229% PA ; -69% MWM, p<0.05). Beneficial effect of oral galactose was seen in STZ-icv rats already after 2 weeks (p<0.005). Following a single galactose load, plasma and CSF galactose concentrations were several times higher following the intraperitoneal (15.74 and 2.3 µM, respectively) than following the oral administration (7.08 and 0.47 µM respectively). Conclusion Plasma and CSF levels of galactose might determine its final effect on the brain due to lower levels elicit after oral than after parenteral galactose administration might account for the beneficial effects of chronic oral galactose treatment on cognitive deficits observed in STZ-icv rat model of sAD. This finding might point to a novel therapeutic strategy in sAD treatment. Acknowledgements Supported by MZOS.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA