1. Ellegood J, Babineau BA, Henkelman RM, Lerch JP, Crawley JN. {{Neuroanatomical analysis of the BTBR mouse model of autism using magnetic resonance imaging and diffusion tensor imaging}}. {Neuroimage};2013 (Apr 15);70:288-300.
Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. Autism-relevant phenotypes in the inbred mouse strain BTBR T+tf/J (BTBR) offer translational tools to discover biological mechanisms underlying unusual mouse behaviors analogous to symptoms of autism. Two of the most consistent findings with BTBR are lack of sociability as measured by the three-chamber social approach task and increased amount of time engaged in self-grooming in an empty cage. Here we evaluated BTBR as compared to two typical inbred strains with high sociability and low self-grooming, C57BL/6J (B6) and FVB/AntJ (FVB), on both the automated three-chambered social approach task and repetitive self-grooming assays. Brains from the behaviorally tested mice were analyzed using magnetic resonance imaging and diffusion tensor imaging to investigate potential neuroanatomical abnormalities throughout the brain; specifically, to discover neuroanatomical mechanisms which could explain the autism-relevant behavioral abnormalities. Significant differences in volume and white matter microstructure were detected in multiple anatomical regions throughout the brain of BTBR compared to B6 and FVB. Further, significant correlations were found between behavioral measures and areas of the brain known to be associated with those behaviors. For example, striatal volume was strongly correlated to time spent in self-grooming across strains. Our findings suggest that neuropathology exists in BTBR beyond the previously reported white matter abnormalities in the corpus callosum and hippocampal commissure and that these brain differences may be related to the behavioral abnormalities seen in BTBR.
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2. Ferder I, Parborell F, Sundblad V, Chiauzzi V, Gomez K, Charreau EH, Tesone M, Dain L. {{Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat}}. {Reproduction};2013;145(4):335-343.
Fragile X mental retardation protein (FMRP) belongs to a small family of RNA-binding proteins. Its absence or inactivity is responsible for fragile X syndrome, the most common cause of inherited mental retardation. Despite its ubiquitous expression, FMRP function and expression remain almost understudied in non-neuronal tissues, though previous studies on germline development during oogenesis may suggest a special function of this protein also in ovarian tissue. In addition, the well-documented association of FMR1 premutation state with fragile X-related premature ovarian insufficiency adds interest to the role of FMRP in ovarian physiology. The aim of the present work was to investigate the expression of Fmr1 mRNA and its protein, FMRP, at different stages of rat follicular development. By immunohistochemical studies we demonstrated FMRP expression in granulosa, theca and germ cells in all stages of follicular development. In addition, changes in Fmr1 expression, both at the protein and mRNA levels, were observed. FMRP levels increased upon follicular development while preantral and early antral follicles presented similar levels of Fmr1 transcripts with decreased expression in preovulatory follicles. These observations suggest that Fmr1 expression in the ovary is regulated at different and perhaps independent levels. In addition, our results show expression of at least four different isoforms of FMRP during all stages of follicular growth with expression patterns that differ from those observed in brain and testis. Our study shows a regulated expression of Fmr1, both at mRNA and protein levels, during rat follicular development.
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3. Huskens B, Verschuur R, Gillesen J, Didden R, Barakova E. {{Promoting question-asking in school-aged children with autism spectrum disorders: Effectiveness of a robot intervention compared to a human-trainer intervention}}. {Dev Neurorehabil};2013 (Apr 15)
Objective: The purpose of the present study was to investigate the effectiveness of an applied behaviour analysis (ABA)-based intervention conducted by a robot compared to an ABA-based intervention conducted by a human trainer in promoting self-initiated questions in children with autism spectrum disorder (ASD). Methods: Data were collected in a combined crossover multiple baseline design across participants. Six children were randomly assigned to two experimental groups. Results: Results revealed that the number of self-initiated questions for both experimental groups increased between baseline and the first intervention and was maintained during follow-up. The high number of self-initiated questions during follow-up indicates that both groups maintained this skill. Conclusions: The interventions conducted by a robot and a human trainer were both effective in promoting self-initiated questions in children with ASD. No conclusion with regard to the differential effectiveness of both interventions could be drawn. Implications of the results and directions for future research are discussed.
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4. Pearson BL, Corley MJ, Vasconcellos A, Blanchard DC, Blanchard RJ. {{Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles}}. {Behav Brain Res};2013 (Apr 15);243:138-145.
Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder.
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5. Turygin N, Matson JL, Konst M, Williams L. {{The relationship of early communication concerns to developmental delay and symptoms of autism spectrum disorders}}. {Dev Neurorehabil};2013 (Apr 15)
Objective: Parental concerns related to communication are an oft-cited reason that children present to early intervention clinics. We examine the relationship between early communication first concerns (FCs) and symptoms of ASD. Methods: The present study included 3173 toddlers at risk for developmental delay. The Battelle Developmental Inventory, 2nd edition and the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) were used to examine developmental quotient scores and autism symptoms. Results: Significant results were observed with respect to FC group and gender. A significant effect of FC-Communication group was observed with respect to developmental quotient overall and subscale scores, as well as autism symptom scores. Conclusion: Those with communication disorders are a heterogeneous population and do not account for all children who will meet criteria for a diagnosis of an ASD.
