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Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
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Amyloid beta modulation of neuronal network activity in vitro
Hamid Charkhkar1, Susheela Meyyappan2, Evgenia Matveeva3
1Electrical and Computer Engineering Department, George Mason University, 4400 University Dr. MSN 1G5, Fairfax, VA 22030, USA.
Brain Research
|October 11, 2015
Summary
This study shows that amyloid-beta 42 oligomers harm neuronal network activity. Methylene blue and memantine protected neurons, suggesting microelectrode array assays can screen Alzheimer's disease therapeutics.
Area of Science:
- Neuroscience
- Biomolecular Science
- Drug Discovery
Background:
- Alzheimer's disease (AD) is linked to amyloid-beta 42 (Aβ42) accumulation.
- In vitro assays are crucial for screening potential therapeutics and accelerating drug development.
- Neuronal cultures on microelectrode arrays (MEAs) offer a functional platform for neurotoxicity assessment.
Purpose of the Study:
- To assess the neurotoxicity of Aβ42 using neuronal cultures on MEAs.
- To investigate the role of glutamate receptors in Aβ42-induced neurotoxicity.
- To evaluate the utility of MEA-based assays for screening Alzheimer's disease therapeutics.
Main Methods:
- Cultured embryonic mouse neurons were seeded on substrate-integrated microelectrode arrays.
- Spontaneous neuronal network activity was recorded via MEA.
- Neurotoxicity of Aβ42 oligomers and monomers was assessed.
- The effects of NMDA and AMPA/kainate receptors were investigated.
- The efficacy of methylene blue (MB) and memantine as therapeutics was tested.
Main Results:
- Aβ42 oligomers, but not monomers, significantly reduced neuronal network spike rate.
- Ionotropic glutamate receptors (NMDA, AMPA/kainate) were implicated in Aβ42's effects.
- Pre-treatment with MB or memantine led to near-complete recovery of neuronal activity within 24 hours after Aβ42 administration.
Conclusions:
- Cultured neuronal networks on MEAs provide a functional assay for Aβ42 neurotoxicity.
- This platform is effective for screening potential therapeutics for Alzheimer's disease.
- MB and memantine demonstrate therapeutic potential in this in vitro model.
