Yu Guo, Minjie Shen, Qiping Dong, Natasha M. Méndez-Albelo, Sabrina X. Huang, Carissa L. Sirois, Jonathan Le, Meng Li, Ezra D. Jarzembowski, Keegan A. Schoeller, Michael E. Stockton, Vanessa L. Horner, André M. M. Sousa, Yu Gao, Birth Defects Research Laboratory, Jon E. Levine, Daifeng Wang, Qiang Chang & Xinyu Zhao
Nature Communications, 26 June 2023
Scientists use Axion’s Maestro MEA to reveal a causal link between elevated MAP1B levels and neuronal pathology and investigate rapamycin as a potential therapeutic for FXS and ASD.
Microtubule proteins (MAPs) are known to impact neuronal development and function. Research suggests that MAP1B plays an important role in fragile X syndrome (FXS) and autism spectrum disorder (ASD), but this relationship is not fully understood. In this study, scientists use a multiplatform approach including Axion’s noninvasive Maestro multielectrode array (MEA) system to show that fragile X messenger ribonucleoprotein1 protein (FMRP) deficiency results in elevated MAP1B levels, which in turn inhibit neuronal maturation in vitro and impair social behaviors in mice. Furthermore, the team found that elevated MAP1B impairs autophagy by reducing autophagosome formation. Importantly, the authors also demonstrated that targeting the autophagy pathway with rapamycin—an FDA-approved drug used in cancer, organ transplantation, and heart disease—rescues the damage caused by high levels of MAP1B, a finding that may lead to the development new therapeutic strategies for FXS and ASD.