1. Chen Q, Zhu YC, Yu J, Miao S, Zheng J, Xu L, Zhou Y, Li D, Zhang C, Tao J, Xiong ZQ. {{CDKL5, a Protein Associated with Rett Syndrome, Regulates Neuronal Morphogenesis via Rac1 Signaling}}. {J Neurosci} (Sep 22);30(38):12777-12786.
Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.
2. Frankel FD, Gorospe CM, Chang YC, Sugar CA. {{Mothers’ reports of play dates and observation of school playground behavior of children having high-functioning autism spectrum disorders}}. {J Child Psychol Psychiatry} (Sep 23)
Background Children with high-functioning autism spectrum disorders (ASD) are generally included with typically developing peers at school. They have difficulties interacting with peers on the school playground. Previous literature suggests that having play dates in the home may be related to better peer acceptance at school. Methods This study examines the relationship between mother-reported play date frequency and amount of conflict, and peer interaction observed on the school playground for a sample of 27 boys and 4 girls meeting structured interview and observation criteria for ASD. Measures of intellectual functioning, adaptive behavior, and social skills were included in a stepwise regression analysis to account for their impact on relationships between maternal play date reports, general peer acceptance at school (as rated by the child’s teacher) and observations of school playground behavior. Results Results revealed that children with autism spectrum disorders who had more play dates in their home tended to spend a greater amount of time engaged in behaviors such as mutual offering of objects, conversing and other turn-taking activities with peers on the school playground. They also received more positive responses to their overtures from peers. These relationships remained highly significant even after accounting for other demographic, general social, and cognitive variables. Conclusions The present results suggest that play date frequency is strongly related to school playground behavior. Owing to the design of this study, future research must assess whether play dates in the home promote better peer relationships on the playground or the reverse. In either case, the assessment of play dates, as well as observation of spontaneous unsupervised social interactions, are important outcome measures to consider in social skills interventions for children with high-functioning ASD.
3. Guenole F, Baleyte JM. {{Effectiveness of Melatonin for Sleep Problems in Autism Spectrum Disorders: Evidence Grows but Research Is Still Needed}}. {J Autism Dev Disord} (Sep 24)
4. Spek AA, Scholte EM, Van Berckelaer-Onnes IA. {{Local Information Processing in Adults with High Functioning Autism and Asperger Syndrome: The Usefulness of Neuropsychological Tests and Self-Reports}}. {J Autism Dev Disord} (Sep 23)
Local information processing in 42 adults with high functioning autism, 41 adults with Asperger syndrome and 41 neurotypical adults was examined. Contrary to our expectations, the disorder groups did not outperform the neurotypical group in the neuropsychological measures of local information processing. In line with our hypotheses, the self-reports did show higher levels of local information processing and a stronger tendency to use systemizing strategies in the two disorder groups. Absent and weak correlations were found between the self-reports and the two neuropsychological tasks in the three groups. The neuropsychological tests and the self-reports seem to measure different underlying constructs. The self-reports were most predictive of the presence of an autism spectrum diagnosis.
