1. Alfawaz HA, Bhat RS, Al-Ayadhi L, El-Ansary AK. {{Protective and restorative potency of Vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups}}. {BMC Complement Altern Med};2014 (Oct 25);14(1):416.
BACKGROUND: Reducing exposure to toxic environmental agents is a critical area of intervention. Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Propionic acid (PA) found in some foods and formed as a metabolic product of gut microbiota has been reported to mediate the effects of autism.Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. The present study investigated the protective and/or therapeutic effects of vitamin D against brain intoxication induced by propionic acid (PPA) in rats. METHODS: Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups of 7. The control group received only phosphate buffered saline; the oral buffered PPA-treated group received a neurotoxic dose of 250 mg/kg body weight/day for 3 days; and the Vitamin D-protected group received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks, after which the rats were injected with PPA 250 mg/Kg body weight/day for 3 days. The fourth group received PPA 250 mg/Kg body weight/day for 3 days followed by alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks (Vitamin D therapeutic effect).Vitamin D and calcium were measured in the plasma of the four studied groups. Serotonin, interferon gamma (IFN-gamma), glutathione-s-transferase activity and DNA double helix breaks were assayed in the brain tissue of the rats for all groups. RESULTS: The obtained data showed that the PPA-treated group demonstrated higher plasma vitamin D levels compared to the control rats, together with multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), an increase in IFN-gamma and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA. CONCLUSIONS: Vitamin D showed a greater protective than therapeutic effect on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration of the impaired biochemically measured parameters representing neurochemical, inflammation, and detoxification processes.
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2. Dillen C, Steyaert J, Op de Beeck HP, Boets B. {{Visual Processing in Adolescents with Autism Spectrum Disorder: Evidence from Embedded Figures and Configural Superiority Tests}}. {J Autism Dev Disord};2014 (Oct 24)
The embedded figures test has often been used to reveal weak central coherence in individuals with autism spectrum disorder (ASD). Here, we administered a more standardized automated version of the embedded figures test in combination with the configural superiority task, to investigate the effect of contextual modulation on local feature detection in 23 adolescents with ASD and 26 matched typically developing controls. On both tasks both groups performed largely similarly in terms of accuracy and reaction time, and both displayed the contextual modulation effect. This indicates that individuals with ASD are equally sensitive compared to typically developing individuals to the contextual effects of the task and that there is no evidence for a local processing bias in adolescents with ASD.
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3. Noriega G. {{A Neural Model to Study Sensory Abnormalities and Multisensory Effects in Autism}}. {IEEE Trans Neural Syst Rehabil Eng};2014 (Oct 16)
Computational modeling plays an increasingly prominent role in complementing critical research in the genetics, neuroscience, and psychology of autism. This paper presents a model that supports the notion that weak central coherence, a processing bias for features and local information, may be responsible for perception abnormalities by failing to « control » sensory issues in autism. The model has a biologically-plausible architecture based on a self-organizing map. It incorporates temporal information in input stimuli, with emphasis on real auditory signals, and provides a mechanism to model multisensory effects. Through comprehensive simulations the paper studies the effect of a control mechanism (akin to central coherence) in compensating the effects of temporal information in the presentation of stimuli, sensory abnormalities, and crosstalk between domains. The mechanism is successful in balancing out timing effects, basic hypersensitivities and, to a lesser degree, multisensory effects. An analysis of the effect of the control mechanism’s onset time on performance, suggests that most of the potential benefits are still attainable even when started rather late in the learning process. This high level of adaptability shown by the neural network highlights the importance of appropriate teaching and intervention throughout the lifetime of persons with autism and other neurological disorders.
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4. Russo A. {{Decreased Mitogen Inducible Gene 6 (MIG-6) Associated with Symptom Severity in Children with Autism}}. {Biomark Insights};2014;9:85-89.
BACKGROUND: Individuals with autism spectrum disorders (ASDs) demonstrate impairment in social interactions and problems in verbal and nonverbal communication. Autism spectrum disorders are thought to affect 1 in 88 children in the US. Recent research has shown that epidermal growth factor receptor (EGFR) activation is associated with nerve cell development and repair. Mitogen inducible gene 6 (MIG-6) is a 58-kDa non-kinase scaffolding adaptor protein consisting of 462 amino-acids, which has been shown to be a negative feedback regulator of EGFR and Met receptor tyrosine kinase (RTK) signaling. SUBJECTS AND METHODS: In this study, we determined plasma levels of MIG-6, which suppresses the EGFR RTK pathway in autistic children, and compared MIG-6 levels with the EGFR ligand, epidermal growth factor (EGF), and the cMET ligand, hepatocyte growth factor (HGF). MIG-6 levels were also compared to the symptom severity of 19 different autistic behaviors. Plasma MIG-6 concentration was measured in 40 autistic children and 39 neurotypical, age, and gender similar controls using an enzyme linked immunosorbent assay (ELISA). Plasma MIG-6 levels were compared to putative biomarkers known to be associated with EGFR and cMET and severity levels of 19 autism related symptoms [awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tip toeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity]. RESULTS: In this study, we found that plasma MIG-6 levels in autistic children (182.41 +/- 24.3 pg/ml) were significantly lower than neurotypical controls (1779.76 +/- 352.5; P = 1.76E – 5). Decreased MIG-6 levels correlated with serotonin, dopamine, Tumor necrosis factor alpha (TNF-alpha), and urokinase receptor (uPAR) concentration, but not with other tested putative biomarkers. MIG-6 levels also correlated significantly with severity of expressive language, receptive language, tip toeing, rocking/pacing, and hand flapping/stimming. CONCLUSIONS: These results suggest a relationship between decreased plasma MIG-6 levels, biomarkers associated with the EGFR pathway, and symptom severity in autism. A strong correlation between plasma MIG-6 and dopamine and serotonin levels suggest that decreased MIG-6 levels may be associated with abnormal neurotransmitter synthesis and/or action. A strong correlation between MIG-6 and uPAR and the inflammatory marker TNF-alpha suggests that low MIG-6 levels may be associated with the HGF/Met signaling pathway, as well as inflammation in autistic children.
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5. Walenski M, Mostofsky SH, Ullman MT. {{Inflectional morphology in high-functioning autism: Evidence for speeded grammatical processing}}. {Res Autism Spectr Disord};2014 (Nov 1);8(11):1607-1621.
Autism is characterized by language and communication deficits. We investigated grammatical and lexical processes in high-functioning autism by contrasting the production of regular and irregular past-tense forms. Boys with autism and typically-developing control boys did not differ in accuracy or error rates. However, boys with autism were significantly faster than controls at producing rule-governed past-tenses (slip-slipped, plim-plimmed, bring-bringed), though not lexically-dependent past-tenses (bring-brought, squeeze-squeezed, splim-splam). This pattern mirrors previous findings from Tourette syndrome attributed to abnormalities of frontal/basal-ganglia circuits that underlie grammar. We suggest a similar abnormality underlying language in autism. Importantly, even when children with autism show apparently normal language (e.g., in accuracy or with diagnostic instruments), processes and/or brain structures subserving language may be atypical in the disorder.
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6. Yoder P, Watson LR, Lambert W. {{Value-Added Predictors of Expressive and Receptive Language Growth in Initially Nonverbal Preschoolers with Autism Spectrum Disorders}}. {J Autism Dev Disord};2014 (Oct 25)
Eighty-seven preschoolers with autism spectrum disorders who were initially nonverbal (under 6 words in language sample and under 21 parent-reported words said) were assessed at five time points over 16 months. Statistical models that accounted for the intercorrelation among nine theoretically- and empirically-motivated predictors, as well as two background variables (i.e., cognitive impairment level, autism severity), were applied to identify value-added predictors of expressive and receptive spoken language growth and outcome. The results indicate that responding to joint attention, intentional communication, and parent linguistic responses were value-added predictors of both expressive and receptive spoken language growth. In addition, consonant inventory was a value-added predictor of expressive growth; early receptive vocabulary and autism severity were value-added predictors of receptive growth.
