L-3-n-Butylphthalide improves synaptic and dendritic spine plasticity and ameliorates neurite pathology in Alzheimer's disease mouse model and cultured hippocampal neurons.

Alzheimer’s disease (AD) is the most common cause of dementia among elderly people. Despite enormous efforts, the pathogenesis of AD still remains unclear and no drug has yet been proved to be disease-modifying. As the basis of learning and memory, the plasticity of synapse and dendritic spine has been impaired during AD progression. Previous studies have showed a protective effect of L-3-n-butylphthalide (L-NBP) on cognitive deficits in AD, we wonder whether this protective effect is associated with positive alterations on synapse and dendritic spines. In this study, we first of all confirmed the anti-dementia effect of L-NBP in 13-month-old APP/PS1 mice, and then investigated the alterations in synaptic and dendritic spine plasticity due to L-NBP treatment both in vivo and in vitro. We also conducted preliminary studies and found the possible mechanisms related to the inhibition of over-activated complement cascade and the remodeling of actin cytoskeleton. Besides, we also found extra benefits of L-NBP on presynaptic dystrophic neurites and attempted to give explanations from the view of autophagy regulation. Taken together, our study added some new evidence to the application of L-NBP in AD treatment and provided deeper insight into the relevant mechanisms for future study.