Huperzine a restores cortico-hippocampal functional connectivity after bilateral AMPA lesion of the nucleus basalis of meynert.

Huperzine A (Hup-A), an alkaloid isolated from Huperzia serrata (Thunb.) Trevis. (Lycopodiaceae), acts as a selective inhibitor of acetylcholinesterase and shows memory-enhancing properties. Although Hup-A has shown promising expectation for Alzheimer's disease (AD) patients, controlled clinical trials supporting its use are limited. The aim of this work was to study in vivo, in an animal model of AD, the pharmacological activity of systemic administration of Hup-A on cortex- and hippocampus-dependent memory. With this purpose, a set of experiments was planned to evaluate attention, learning, working and spatial memory with respect to cortical and hippocampal electroencephalogram (EEG) theta rhythm during the object recognition test and Morris water maze in animals with lesion of the nucleus basalis of Meynert (NBM). In NBM-lesioned animals, compared with control, an increased theta power in the cortex and a reduced theta rhythm oscillation in the hippocampus were found. These EEG changes were correlated with worse performance in learning and memory tasks. In rats with damaged NBM, Hup-A (0.5 mg/kg i.p.) was able to restore EEG architecture, producing cortical desynchronization and reduction in theta power, while in the hippocampus the drug increased theta oscillation and reduced the impairment in attention/working memory as well as spatial navigation performance in the behavioral tasks. Taken together, the present data suggest that Hup-A is able to restore cholinergic cortico-hippocampal functional connectivity. In conclusion, the present results are in agreement with other experimental evidence that promote the clinical use of this natural drug.