1. Cef E, van den Berg WE, Ram B, Jaafar IA, Nieuwenhuizen-Bakker IM, Gasparini F, Kushner SA, Willemsen R. {{Fragile X mice have robust mGluR5-dependent alterations of social behaviour in the Automated Tube Test}}. {Neurobiology of disease}. 2015 Jan 3.
Fragile X syndrome is the most common monogenetic form of intellectual disability and autism. Although the Fmr1 knockout mouse model recapitulates many aspects of the human FXS condition, the establishment of robust social behavioural phenotypes suitable for drug screening has been difficult. Here, we describe a novel social behavioural paradigm, the Automated Tube Test (ATT), for which Fmr1 knockout mice demonstrate a highly reliable and robust phenotype. Fmr1 KO mice show highly dominant behaviour over wild-type littermates in the ATT. Consistent with previous findings, we observed a highly significant, albeit partial, rescue of the altered social behaviour of Fmr1 knockout mice in the ATT, using genetic (mGluR5 deletion) or pharmacological inhibition (mGluR5 antagonist) of mGluR5 signalling independently. Together, our results validate the Automated Tube Test as a robust outcome measure for social behaviour in preclinical research for FXS, and confirm the pathophysiological relevance of mGluR5 signalling. Moreover, our findings highlight the strategy of initiating pharmacological intervention in adulthood as holding significant clinical potential.
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2. Roley SS, Mailloux Z, Parham LD, Schaaf RC, Lane CJ, Cermak S. {{Sensory integration and praxis patterns in children with autism}}. {The American journal of occupational therapy : official publication of the American Occupational Therapy Association}. 2015 Jan-Feb;69(1):6901220010p1-8.
OBJECTIVE. We sought to characterize sensory integration (SI) and praxis patterns of children with autism spectrum disorder (ASD) and discern whether these patterns relate to social participation. METHOD. We extracted Sensory Integration and Praxis Tests (SIPT) and Sensory Processing Measure (SPM) scores from clinical records of children with ASD ages 4-11 yr (N = 89) and used SIPT and SPM standard scores to describe SI and praxis patterns. Correlation coefficients were generated to discern relationships among SI and praxis scores and these scores’ associations with SPM Social Participation scores. RESULTS. Children with ASD showed relative strengths in visual praxis. Marked difficulties were evident in imitation praxis, vestibular bilateral integration, somatosensory perception, and sensory reactivity. SPM Social Participation scores were inversely associated with areas of deficit on SIPT measures. CONCLUSION. Children with ASD characteristically display strengths in visuopraxis and difficulties with somatopraxis and vestibular functions, which appear to greatly affect participation.
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3. Uno Y, Uchiyama T, Kurosawa M, Aleksic B, Ozaki N. {{Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder}}. {Vaccine}. 2015 Jan 3.
OBJECTIVE: This case-control study investigated the relationship between the risk of Autism Spectrum Disorder (ASD) onset, and early exposure to the combined Measles-Mumps-Rubella (MMR) vaccine and thimerosal consumption measured from vaccinations in the highly genetically homogenous Japanese population. METHODS: Vaccination histories at 1, 3, 6, 12, 18, 24, and 36 months from birth were investigated in ASD cases (189 samples), and controls (224 samples) matching age and sex in each case. Crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to determine relationship between MMR vaccination and ASD. The differences in mean values of the thimerosal dosage between cases and controls were analyzed using an unpaired t-test. MMR vaccination and thimerosal dosage were also investigated using a conditional multiple-regression model. RESULTS: There were no significant differences in MMR vaccination and thimerosal dosage between cases and controls at any age. Furthermore, the ORs (95% CIs) of MMR vaccination and thimerosal dosage associated with ASD in the conditional multiple regression model were, respectively, 0.875 (0.345-2.222) and 1.205 (0.862-1.683) at age 18 months, 0.724 (0.421-1.243) and 1.343 (0.997-1.808) at 24 months, and 1.040 (0.648-1.668) and 0.844 (0.632-1.128) at 36 months. Thus, there were no significant differences. CONCLUSIONS: No convincing evidence was found in this study that MMR vaccination and increasing thimerosal dose were associated with an increased risk of ASD onset.
