Authors: Anna Flury, Leen Aljayousi, Hye-Jin Park, Mohammadparsa Khakpour, Jack Mechler, Siaresh Aziz, Jackson D. McGrath, Pragney Deme, Colby Sandberg, Fernando González Ibáñez, Olivia Braniff, Thi Ngo, Simira Smith, Matthew Velez, Denice Moran Ramirez, Dvir Avnon-Klein, John W. Murray, Jia Liu, Martin Parent, Susana Mingote, Norman J. Haughey, Sebastian Werneburg, Marie-Ève Tremblay, and Pinar Ayata
Neuron, 23 December 2024
Scientists use Axion BioSystems’ next-generation Maestro Pro MEA system to assess neuron functionality in vitro and explore a potential therapeutic target to prevent or slow neurodegeneration.
Microglia, the brain’s immune cells, have been implicated in Alzheimer's disease (AD) and other neurodegenerative diseases, but the underlying pathophysiological mechanisms are not fully understood. In this study, researchers explore the role of the integrated stress response (ISR), a microglial signaling pathway that may contribute to neurodegeneration. To assess neuron functionality when exposed to conditioned media from ISR-activated microglia—also known as “dark” microglia due to their unique ultrastructural characteristics observed under electron microscopy—the team used Axion BioSystems’ noninvasive Maestro Pro multielectrode array (MEA) system and found that ISR-activated microglia secrete toxic lipids which were observed to cause neuronal toxicity, suggesting ISR-activated microglia as a novel neurodegenerative phenotype. Importantly, inhibiting ISR or lipid synthesis mitigates synapse loss in AD models. Overall, according to the authors, this research “delineates a potentially druggable microglial phenotype whose functional outcome is neurodegenerative and expands our knowledge on the repertoire of microglial mechanisms of neurotoxicity.”
