title: Amyloid beta modulation of neuronal network activity in vitro.
abstract: In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid-β 1-42 (Aβ42), a biomolecule implicated in the Alzheimer׳s disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. Aβ42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of Aβ42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24h after administration of Aβ42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for Aβ induced changes in neurological function.
authors.affiliation: Electrical and Computer Engineering Department, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA. Electronic address: hamid.charkhkar@case.edu.
authors.forename: Hamid
authors.initials: H
authors.lastname: Charkhkar
authors.affiliation: Department of Bioengineering, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
authors.forename: Susheela
authors.initials: S
authors.lastname: Meyyappan
authors.affiliation: Adlyfe Inc., 9430 Key West Avenue, Suite 219, Rockville, MD 20850, USA.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Matveeva
authors.affiliation: Adlyfe Inc., 9430 Key West Avenue, Suite 219, Rockville, MD 20850, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Moll
authors.affiliation: Department of Molecular Neuroscience, The Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: McHail
authors.affiliation: Electrical and Computer Engineering Department, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
authors.forename: Nathalia
authors.initials: N
authors.lastname: Peixoto
authors.affiliation: System of Systems Analytics, Inc. (SoSACorp), 11250 Waples Mill Road, Fairfax, VA 22030, USA.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cliff
authors.affiliation: Department of Bioengineering, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Pancrazio
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity*; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D008559:Memantine
keywords: Alzheimer׳s disease; Amyloid beta; Functional assay; In vitro models; Microelectrode array; Neuronal networks