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Neural Plasticity
Volume 2012, Article ID 976164, 9 pages
http://dx.doi.org/10.1155/2012/976164
Research Article

Hippocampal CA1 Pyramidal Neurons of Mecp2 Mutant Mice Show a Dendritic Spine Phenotype Only in the Presymptomatic Stage

1Department of Neurobiology, Civitan International Research Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
2Department of Neuroscience, University of Torino and National Institute of Neuroscience, Turin 10126, Italy
3Neuroscience Institute, CNR, Pisa 56125, Italy
4IFEC-CONICET and Department of Pharmacology, School of Chemical Sciences, Cordoba National University, Cordoba 5000, Argentina
5Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA

Received 15 March 2012; Accepted 23 May 2012

Academic Editor: Hansen Wang

Copyright © 2012 Christopher A. Chapleau et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alterations in dendritic spines have been documented in numerous neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, an X chromosome-linked disorder associated with mutations in MECP2, is the leading cause of intellectual disabilities in women. Neurons in Mecp2-deficient mice show lower dendritic spine density in several brain regions. To better understand the role of MeCP2 on excitatory spine synapses, we analyzed dendritic spines of CA1 pyramidal neurons in the hippocampus of male mutant mice by either confocal microscopy or electron microscopy (EM). At postnatal-day 7 (P7), well before the onset of RTT-like symptoms, CA1 pyramidal neurons from mutant mice showed lower dendritic spine density than those from wildtype littermates. On the other hand, at P15 or later showing characteristic RTT-like symptoms, dendritic spine density did not differ between mutant and wildtype neurons. Consistently, stereological analyses at the EM level revealed similar densities of asymmetric spine synapses in CA1 stratum radiatum of symptomatic mutant and wildtype littermates. These results raise caution regarding the use of dendritic spine density in hippocampal neurons as a phenotypic endpoint for the evaluation of therapeutic interventions in symptomatic Mecp2-deficient mice. However, they underscore the potential role of MeCP2 in the maintenance of excitatory spine synapses.