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Brain Res. 2015 Dec 10;1629:1-9. doi: 10.1016/j.brainres.2015.09.036. Epub 2015 Oct 14.

Amyloid beta modulation of neuronal network activity in vitro.

Author information

1
Electrical and Computer Engineering Department, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA. Electronic address: hamid.charkhkar@case.edu.
2
Department of Bioengineering, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
3
Adlyfe Inc., 9430 Key West Avenue, Suite 219, Rockville, MD 20850, USA.
4
Department of Molecular Neuroscience, The Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA.
5
Electrical and Computer Engineering Department, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
6
System of Systems Analytics, Inc. (SoSACorp), 11250 Waples Mill Road, Fairfax, VA 22030, USA.

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.

KEYWORDS:

Alzheimer׳s disease; Amyloid beta; Functional assay; In vitro models; Microelectrode array; Neuronal networks

PMID:
26453830
DOI:
10.1016/j.brainres.2015.09.036
[Indexed for MEDLINE]

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