Reference : MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy d...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/27273
MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain
English
Nguyen, Minh Vu Chong mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
Du, Fang [Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, United States]
Felice, Christy A. [Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, United States]
Shan, Xiwei [Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, United States]
Nigam, Aparna [Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, United States]
Mandel, Gail [Vollum Institute and Howard Hughes Medical Institute, Oregon Health and Science University, Portland, OR 97239, United States]
Robinson, John K. [Department of Psychology, Stony Brook University, Stony Brook, NY 11794, United States]
Ballas, Nurit [Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, United States]
2012
Journal of Neuroscience
32
29
10021-10034
Yes (verified by ORBilu)
International
02706474
[en] AMPA receptor ; Golgi stain ; Rett syndrome ; Western blotting ; Animals ; Brain ; Dendrites ; Disease Models, Animal ; Gene Expression Regulation ; Male ; Methyl-CpG-Binding Protein 2 ; Mice ; Mice, Transgenic ; Motor Activity ; Nerve Net ; Neurons ; Rett Syndrome ; Synapses
[en] Mutations in the X-linked gene, methyl-CpG binding protein 2 (Mecp2), underlie a wide range of neuropsychiatric disorders, most commonly, Rett Syndrome (RTT), a severe autism spectrum disorder that affects approximately one in 10,000 female live births. Because mutations in the Mecp2 gene occur in the germ cells with onset of neurological symptoms occurring in early childhood, the role of MeCP2 has been ascribed to brain maturation at a specific developmental window. Here, we show similar kinetics of onset and progression of RTT-like symptoms in mice, including lethality, if MeCP2 is removed postnatally during the developmental stage that coincides with RTT onset, or adult stage. For the first time, we show that brains that lose MeCP2 at these two different stages are actively shrinking, resulting in higher than normal neuronal cell density. Furthermore, we show that mature dendritic arbors of pyramidal neurons are severely retracted and dendritic spine density is dramatically reduced. In addition, hippocampal astrocytes have significantly less complex ramified processes. These changes accompany a striking reduction in the levels of several synaptic proteins, including CaMKII α/β, AMPA, and NMDA receptors, and the synaptic vesicle proteins Vglut and Synapsin, which represent critical modifiers of synaptic function and dendritic arbor structure. Importantly, the mRNA levels of these synaptic proteins remains unchanged, suggesting that MeCP2 likely regulates these synaptic proteins post-transcriptionally, directly or indirectly. Our data suggest a crucial role for MeCP2 in post-transcriptional regulation of critical synaptic proteins involved in maintaining mature neuronal networks during late stages of postnatal brain development. © 2012 the authors.
http://hdl.handle.net/10993/27273
10.1523/JNEUROSCI.1316-12.2012

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