Rigby MJ, Orefice NS, Lawton AJ, Ma M, Shapiro SL, Yi SY, Dieterich IA, Frelka A, Miles HN, Pearce RA, Yu JPJ, Li L, Denu JM, and Puglielli L.
Bioelectronic assays and other methods support relationship between overexpression of SLC25A1 and autism spectrum disorder in mouse models
Evidence suggests a link between the development of autism spectrum disorder (ASD) and abnormal intracellular citrate/acetyl-coenzyme A (acetyl-CoA) flux, likely related to changes in endoplasmic reticulum (ER)-based Nɛ-lysine acetylation. In this study, scientists generated an neuron transgenic (nTg) mouse model with SLC25A1 overexpression in the forebrain neurons to investigate the link between abnormal cytosolic-to-endoplasmic reticulum acetyl-CoA flux and the development of an autistic-like phenotype.
Overall results from the multiplatform study—which demonstrated autistic-like behaviors in mice, disrupted white matter, altered synaptic structure and function, and differential changes in the proteome and acetyl-proteome—support an association between ASD and abnormal intracellular flux. To noninvasively explore neural activity in the SLC25A1 nTg primary neurons in vitro, the scientists used Axion’s Maestro Pro multielectrode array (MEA) platform. The data revealed increased dendritic branching, dendritic spine volume, and synaptic density, as well as an increase in neural excitability.