Huperzine A Restores Cortico-Hippocampal Functional Connectivity after Bilateral AMPA Lesion of the Nucleus Basalis of Meynert

Article type: Research Article

Authors: Rispoli, Vincenzo^{a; *} | Ragusa, Salvatore^a | Nisticò, Robert^{b; c} | Marra, Rosario^e | Russo, Emilio^d | Leo, Antonio^a | Felicitá, Vera^a | Rotiroti, Domenicantonio^a

Affiliations: [a] Laboratory for Preclinical Researches in Neuropharmacology and Neurodegenerative Diseases, Department of “Health Sciences”, University Magna Graecia of Catanzaro, Italy | [b] IRCSS Santa Lucia Foundation, Rome, Italy | [c] Department of Physiology and Pharmacology, Sapienza University of Rome, Italy | [d] Clinical Pharmacology Unit, Department of Health Sciences School of Medicine, University Magna Graecia of Catanzaro, Italy | [e] Institute for Neurological Sciences, Pharmacological Section, National Council of Researches, Catanzaro, Italy

Correspondence: [*] Correspondence to: Vincenzo Rispoli, MD, Department of Health Sciences, University Magna Græcia of Catanzaro, University campus “Salvatore Venuta”, Viale Europa (loc Germaneto), 88100 Catanzaro, Italy. Tel.: +39 0961 3695735; Fax: +39 0961 391490; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer's disease, attention, cholinesterase inhibitors, electroencephalography, hippocampus, huperzine a, learning, memory, nucleus basalis of meynert

DOI: 10.3233/JAD-130278

Journal: Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 833-846, 2013