caa a22 4500 606201319 CHVBK 20210128100947.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0664-x doi (NATIONALLICENCE)springer-10.1007/s00429-013-0664-x MeCP2-mediated alterations of striatal features accompany psychomotor deficits in a mouse model of Rett syndrome [Elektronische Daten] [Fang-Chi Kao, San-Hua Su, Gregory Carlson, Wenlin Liao] Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Affected individuals develop motor deficits including stereotypic hand movements, impaired motor learning and difficulties with movement. To understand the neural mechanisms of motor deficits in RTT, we characterized the molecular and cellular phenotypes in the striatum, the major input nucleus of the basal ganglia that controls psychomotor function, in mice carrying a null allele of Mecp2. These mice showed significant hypoactivity associated with impaired motor coordination and motor skill learning. We found that dopamine content was significantly reduced in the striatum of Mecp2 null mice. Reduced dopamine was accompanied by down-regulation of tyrosine hydroxylase and up-regulation of dopamine D2 receptors, particularly in the rostral striatum. We also observed that loss of MeCP2 induced compartment-specific alterations in the striatum, including reduced expression of μ-opioid receptors in the striosomes and increased number of calbindin-positive neurons in the striatal matrix. The total number of parvalbumin-positive interneurons and their dendritic arborization were also significantly increased in the striatum of Mecp2 null mice. Together, our findings support that MeCP2 regulates a unique set of genes critical for modulating motor output of the striatum, and that aberrant structure and function of the striatum due to MeCP2 deficiency may underlie the motor deficits in RTT. Springer-Verlag Berlin Heidelberg, 2013 Autism spectrum disorders nationallicence Striatum nationallicence Dopamine nationallicence μ-Opioid receptor nationallicence Calbindin nationallicence Parvalbumin nationallicence Kao Fang-Chi Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut Su San-Hua Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut Carlson Gregory Department of Psychiatry, University of Pennsylvania, 19104, Philadelphia, PA, USA aut Liao Wenlin Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 419-434 1863-2653 220:1<419 2015 220 429 https://doi.org/10.1007/s00429-013-0664-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0664-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kao Fang-Chi Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut NATIONALLICENCE 700 1- Su San-Hua Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut NATIONALLICENCE 700 1- Carlson Gregory Department of Psychiatry, University of Pennsylvania, 19104, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Liao Wenlin Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, Chi-Nan Road, Wen-Shan District, 11605, Taipei, Taiwan aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 419-434 1863-2653 220:1<419 2015 220 429