Tau Expresion in Frontal Cortex of Streptozotocin Intracerebroventriculae Treated Rats

TAU PROTEIN EXPRESION IN FRONTOPARIETAL CORTEX OF EXPERIMENTAL RAT MODEL OF SPORADIC ALZHEIMER’S DISEASE

Jelena Osmanović1, Melita Šalković-Petrišić1, Peter Riederer2,

1Department of Pharmacology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Salata 11, HR 10 000 Zagreb, Croatia; 2Department of Clinical Neurochemistry, University Department of Psychiatry and Psychotherapy, University of Würzburg, Fuechsleinstr. 15, 97080 Würzburg, Germany

Objectives

Neurofibrillar tangles are one of the major hallmarks of sporadic Alzheimer disease (sAD). They are associated with tau protein hyperphosphorylation which could happen due to imbalance in its phosphorylation/dephosphorylation status. Glycogen synthase kinase 3 which is involved in tau protein phosphorylation has bee found altered both in human sAD and in its experimental model, streptozotocin-intracerebroventricularly (STZ-icv) treated rats. In STZ-icv rat tau protein was measured in hippocampus only where increased total and phospho(p)-tau was found. Research was aimed to investigate the possible changes of tau protein in the frontoparietal cortex (FC) of STZ-icv rats one and three months following the treatment.

Design and Methods

Adult male Wistar rats were treated icv with a single STZ dose (1 mg/kg) while the controls received vehicle only. Cognitive functions were tested by Morrris Water Maze Swimming Test. Expression of total and p-tau protein was measured by SDS-PAGE/Western blot. Data were analysed by Mann-Whitney U test (p<0.05).

Results

Deficits in learning and memory functions were found both after 1 and 3 months following the STZ icv treatments (p<0.05). Decreased levels of total tau (74,9%) and p-tau (49,65%) (p<0.05) were found in FC after one month while three months after the treatment both tau values were comparable to the control ones.

Conclusion

Results suggest that STZ-icv induced changes of tau protein in FC are time dependent and regarding the increased tau phosphorylation reported in STZ-icv rat hippocampus they also seem to be brain-region dependent. Since changes found in human sAD refer mostly to the advanced stage of the disease while early changes are mystery. The possibility of similar tau protein alterations in human FC at the beginning of sAD could not be excluded.

Supported by Croatian MZOS (108-1080003-0020) and DAAD.