Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice

Manigandan Krishnan¹Ayishal B Mydeen²Mohammed Nakhal²Marwa F Ibrahim²Richardjayaraj Lawrencejayaraj¹Milos R Ljubisavljevic³Mohammad I. K. Hamad^2*Fatima Yousif Ismail^1,4*

• ¹Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
• ²Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
• ³Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
• ⁴Department of Neurology and Neurosurgery, School of Medicine, Johns Hopkins Medicine, Baltimore, Maryland, United States

Mutations in the methyl-CpG-binding protein-2 gene (MECP2), which cause Rett syndrome (RTT), disrupts neuronal activity; however, the impact of MECP2 loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons — crucial for spatial memory and learning —remain poorly understood. In this study, we utilized Golgi staining and neuron tracing in Mecp2+/- mouse model of RTT to investigate the pyramidal and stellate cells alterations in MECII. Our findings revealed that pyramidal cells displayed a significant reduction in apical dendritic length, soma size and spine density, while basal dendrites showed increased dendritic complexity and branching. On the other hand, stellate cells exhibited dendritic hypertrophy along with increased soma size, primary dendrites and localized increase in dendritic intersections, despite an overall reduction in total dendritic length and spine density. These findings underscore the notion that MECP2 loss-of-function can disrupt MECII pyramidal and stellate cells cytoarchitecture in a cell-type-specific manner, emphasizing its critical role in maintaining proper dendritic morphology in circuits which is crucial for learning and memory.