title: Curcumin protects organotypic hippocampal slice cultures from Aβ1-42-induced synaptic toxicity.
abstract: Increasing evidence demonstrates that beta-amyloid (Aβ) is toxic to synapses, resulting in the progressive dismantling of neuronal circuits. Counteract the synaptotoxic effects of Aβ could be particularly relevant for providing effective treatments for Alzheimer's disease (AD). Curcumin was recently reported to improve learning and memory in animal models of AD. Little is currently known about the specific mechanisms by which Aβ affects neuronal excitability and curcumin ameliorates synaptic transmission in the hippocampus. Organotypic hippocampal slice cultures exposed to Aβ1-42 were used to study the neuroprotective effects of curcumin through a spectral analysis of multi-electrode array (MEA) recordings of spontaneous neuronal activity. Curcumin counteracted both deleterious effects of Aβ; the initial synaptic dysfunction and the later neuronal death. The analysis of MEA recordings of spontaneous neuronal activity showed an attenuation of signal propagation induced by Aβ before cell death and curcumin-induced alterations to local field potential (LFP) phase coherence. Curcumin-mediated attenuation of Aβ-induced synaptic dysfunction involved regulation of synaptic proteins, namely phospho-CaMKII and phospho-synapsin I. Taken together, our results expand the neuroprotective role of curcumin to a synaptic level. The identification of these mechanisms underlying the effects of curcumin may lead to new targets for future therapies for AD.
authors.affiliation: Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6UB, UK; Laboratory of Neuroprotection and Cell Signalling, Department of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil. Electronic address: juhoppe@hotmail.com.
authors.forename: Juliana Bender
authors.initials: JB
authors.lastname: Hoppe
authors.forename: Marcus
authors.initials: M
authors.lastname: Haag
authors.forename: Benjamin Jason
authors.initials: BJ
authors.lastname: Whalley
authors.forename: Christianne Gazzana
authors.initials: CG
authors.lastname: Salbego
authors.forename: Helena
authors.initials: H
authors.lastname: Cimarosti
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D016704:Synapsins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D016704:Synapsins; C075222:amyloid beta-protein (1-42); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D003474:Curcumin
keywords: Beta-amyloid peptide; CaMKII; Curcumin; Multi-electrode array; Organotypic hippocampal slice culture; Synapsin I