1. Cusmano DM, Mong JA. {{In utero exposure to valproic Acid changes sleep in juvenile rats: a model for sleep disturbances in autism}}. {Sleep}. 2014; 37(9).
STUDY OBJECTIVES: To determine whether sleep disturbances are found in the valproic acid model of autism spectrum disorders (ASD). DESIGN: Comparative study for sleep behavior, sleep architecture, electroencephalogram (EEG) spectral analysis, and glutamic acid decarboxylase (GAD) 65/67 protein expression in juvenile rats exposed to valproic acid (VPA), sodium salt, or saline in utero. SETTING: N/A. PARTICIPANTS: Juvenile (postnatal day 32) male and female Sprague- Dawley rats. INTERVENTIONS: In utero exposure to either saline or 400 mg/kg VPA administered intraperitoneally to the dams on gestational day 12.5. On postnatal days 22-24, all rats were implanted with transmitters to record EEG and electromyogram (EMG) activity. MEASUREMENTS AND RESULTS: During the light phase, when nocturnal animals are typically quiescent, the VPA-exposed animals spent significantly more time in wake ( approximately 35 min) and significantly less time in non-rapid eye movement (NREM) sleep ( approximately 26 min) compared to the saline controls. Furthermore, spectral analysis of the EEG reveled that VPA-exposed animals exhibited increased high-frequency activity during wake and rapid eye movement (REM) sleep and reduced theta power across all vigilance states. Interestingly, the gamma-aminobutyric acid (GABA)-ergic system, which modulates the induction and maintenance of sleep states, was also disrupted, with reduced levels of both GAD 65 and GAD67 in the cortical tissue of VPA-exposed animals compared to saline controls. CONCLUSIONS: To date, the current animal models of ASD have been underutilized in the investigation of associated sleep disturbances. The VPA animal model recapitulates aspects of sleep disruptions reported clinically, providing a tool to investigate cellular and molecular dysregulation contributing to sleep disruptions in ASD.
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2. Isshiki M, Tanaka S, Kuriu T, Tabuchi K, Takumi T, Okabe S. {{Enhanced synapse remodelling as a common phenotype in mouse models of autism}}. {Nat Commun}. 2014; 5: 4742.
Developmental deficits in neuronal connectivity are considered to be present in patients with autism spectrum disorders (ASDs). Here we examine this possibility by using in vivo spine imaging in the early postnatal cortex of ASD mouse models. Spines are classified by the presence of either the excitatory postsynaptic marker PSD-95 or the inhibitory postsynaptic marker gephyrin. ASD mouse models show consistent upregulation in the dynamics of PSD-95-positive spines, which may subsequently contribute to stable synaptic connectivity. In contrast, spines receiving inputs from the thalamus, detected by the presence of gephyrin clusters, are larger, highly stable and unaffected in ASD mouse models. Importantly, two distinct mouse models, human 15q11-13 duplication and neuroligin-3 R451C point mutation, show highly similar phenotypes in spine dynamics. This selective impairment in dynamics of PSD-95-positive spines receiving intracortical projections may be a core component of early pathological changes and be a potential target of early intervention.
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3. Key AP, Corbett BA. {{ERP Responses to Face Repetition During Passive Viewing: A Nonverbal Measure of Social Motivation in Children With Autism and Typical Development}}. {Dev Neuropsychol}. 2014; 39(6): 474-95.
This study examined whether individual differences in social motivation affect the extent of processing of social versus nonsocial information. Event-related potentials were recorded in 13 children with autism spectrum disorder and 11 typically developing children during passive viewing of unfamiliar faces and houses. One image in each category was presented repeatedly, the rest were shown once. Analyses indicated no group differences in the early perceptual responses. Only typical children evidenced larger P600 for the repeated faces. These results were replicated during a retest session. Individual differences in memory for the repeated faces correlated with standardized behavioral assessments of social skills.
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4. Motil KJ, Barrish JO, Neul JL, Glaze DG. {{Low bone mineral mass is associated with decreased bone formation and diet in girls with rett syndrome}}. {J Pediatr Gastroenterol Nutr}. 2014; 59(3): 386-92.
OBJECTIVE: The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. METHODS: Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. RESULTS: Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. CONCLUSIONS: The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.
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5. Nair MK, Russell PS, George B, Prasanna GL, Bhaskaran D, Leena ML, Russell S, Mammen P. {{CDC Kerala 9: Effectiveness of Low Intensity Home Based Early Intervention for Autism Spectrum Disorder in India}}. {Indian J Pediatr}. 2014.
OBJECTIVE: To validate effectiveness of low intensity, home based early intervention (EI) models in autism for countries with low disability resources. METHODS: Fifty-two toddlers and young children were assessed before and after intervention with Childhood Autism Rating Scale, Vineland Social Maturity Scale, and Receptive-Expressive Emergent Language Scale. Developmental and speech therapists helped mothers assemble low-cost training kits based on the developmental age of the child, gave initial training in the basic behavioral technique to address the three autism symptom clusters at home. Follow-up support was given either on a weekly, fortnightly or monthly basis. Most of the children were also placed in play-schools. Data was analyzed using appropriate bivariate and multivariate techniques. RESULTS: There was statistical and clinical amelioration in the severity of autism, with acquisition of social skills and language skills (all P = 0.001) after intervention in children with mild to severe autism. Gender showed a trend in becoming a significant predictor for intervention response. CONCLUSIONS: Low-intensity, home-based EI can be effectively used in situations where there is paucity of disability resources in countries like India, especially in primary-care and community settings.
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6. Sato A, Kasai S, Kobayashi T, Takamatsu Y, Hino O, Ikeda K, Mizuguchi M. {{[Participation of mTOR signal system in autistic behavior of mice modeling tuberous sclerosis]}}. {Nihon Shinkei Seishin Yakurigaku Zasshi}. 2014; 34(2): 51-2.
