Dendritic spine dysgenesis in Rett syndrome.

Xin Xu,Lucas Pozzo-Miller,Eric C Miller

doi:10.3389/fnana.2014.00097

Xin Xu, Lucas Pozzo-Miller + Show 1 more

Open Access

https://doi.org/10.3389/fnana.2014.00097

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Abstract

Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). Here, we review the evidence demonstrating that principal neurons in RTT individuals and Mecp2-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders.

Highlights

Espinas dendríticas are small cytoplasmic extensions emerging from the dendrites of neurons that were first described in the cerebellum and cerebrum of birds and mammals by Santiago Ramón y Cajal at the end of the 19th century (Ramón y Cajal, 1888, 1891b, 1896; as cited in Yuste, 2010)
Rett syndrome (RTT) is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2)
We discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by methyl CpG-binding protein 2 (MeCP2), offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders

Summary

Dendritic spine dysgenesis in Rett syndrome

Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (MECP2). We review the evidence demonstrating that principal neurons in RTT individuals and Mecp2based experimental models exhibit alterations in the number and morphology of dendritic spines. We discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other MECP2-associated neurodevelopmental disorders

INTRODUCTION

Hippocampus Cortex Hippocampus Cortex Hippocampus Cortex Hippocampus

CONCLUSION