Protective effect of the heparin-derived oligosaccharide C3, on AF64A-induced cholinergic lesion in rats

Alzheimer's disease (AD) literature indicates that glycosaminoglycans (GAGs) may prevent proteoglycan-induced amyloid-beta (Abeta) aggregation, decrease Abeta-induced tau-2 immunoreactivity, and increase the axonal growth and arborization of hippocampal neurons. However, there is no information about the impact of GAGs on cholinergic lesions. Here, AF64A was administered stereotaxically into the lateral ventricles of rats, at doses that are selective for cholinotoxicity (1 and 2 nmol). The heparin-derived oligosaccharide (HDO), C3 (25mg/kg), was administered orally, once daily for 7 days before, and 7 days after AF64A administration. Choline acetyltransferase (ChAT) immunohistochemistry revealed that C3 administration reduced AF64A-induced cholinergic damage in the septum and cingulum bundle. Quantitative neuronal cell counts showed that C3 attenuated, by 60%, the decrease in cell number in the medial septum. Enzyme analysis showed that C3 also significantly restored ChAT (30%) and acetylcholinesterase (AChE) enzyme activity (45%), which had been diminished by AF64A. Our data suggest that, in addition to its effects of anti-Abeta aggregation, anti-Abeta-induced tau-2 immunoreactivity, and neurotrophic effects, C3 also effectively reduces AF64A-induced cholinergic damage; hence it may have potential therapeutic value in AD patients.