Developmental and maintenance defects in Rett syndrome neurons identified by a new mouse staging system in vitro

Frontiers in Cellular Neuroscience

Angela ePatrizio¹  Enrico eTongiorgi¹  Alberto eMontalbano¹  Marina eSciancalepore¹  Gabriele eBaj¹ 

[1] University of Trieste;

关键词: Dendrites;    Dendritic Spines;    Rett Syndrome;    neurodevelopment;    hippocampal neurons;    Neuronal morphology;   

DOI  :  10.3389/fncel.2014.00018

来源: DOAJ

【 摘 要 】

Rett Syndrome (RTT) is a neurodevelopmental disorder associated with intellectual disability, mainly caused by loss-of-function mutations in the MECP2 gene. RTT brains display decreased neuronal size and dendritic arborisation possibly caused by either a developmental failure or a deficit in the maintenance of dendritic arbour structure. To distinguish between these two hypotheses, the development of Mecp2-knockout mouse hippocampal neurons was analyzed in vitro. Since a staging system for the in vitro development of mouse neurons was lacking, mouse and rat hippocampal neurons development was compared between 1-15 days in vitro (DIV) leading to a 6-stage model for both species. Mecp2-knockout hippocampal neurons displayed reduced growth of dendritic branches from stage 4 (DIV4) onwards. At stages 5-6 (DIV9-15), synapse number was lowered in Mecp2-knockout neurons, suggesting increased synapse elimination. These results point to both a developmental and a maintenance setback affecting the final shape and function of neurons in RTT.

【 授权许可】

Unknown