Donepezil promotes the proliferation of neural stem cells in the dentate gyrus of aged mice

Abstract

rivastigmine treatment of degenerating primary neurons promoted survival (Bailey and Lahiri, 2010). Both drugs increased neuronal and synaptic markers, and immunocytochemistry showed preservation of neuronal morphology with both drugs. Memantine reduced levels of Ab42 secretion in primary cells, and reduced soluble Ab42 levels in the cortices of transgenic mice. These drugs are now being tested in primary lymphocyte cultures from human subjects, and other mechanistic studies are ongoing. Conclusions: The responses to memantine and rivastigmine treatment observed in these different models are not identical, though there are important similarities with potentially important implications for current and future therapeutic interventions for AD. Both drugs increased or preserved cellular viability, neuronal morphology and possibly synaptic transmission in degenerating primary neurons, in addition to preserving synaptic markers that are reduced in AD. These drugs were shown to alter APP processing in cell culture and animal models, though the response varied between models. APP and Ab are associated with neurite and synapse regulation, so taken together, these results imply common or synergistic modes of action that could be further explored for the development of improved therapeutic agents.