1. De Filippis B, Ricceri L, Fuso A, Laviola G. {{Neonatal exposure to low dose corticosterone persistently modulates hippocampal mineralocorticoid receptor expression and improves locomotor/exploratory behavior in a mouse model of Rett syndrome}}. {Neuropharmacology};2012 (Jun 15)
Rett syndrome (RTT) is a pervasive neurodevelopmental disorder, primarily affecting girls. RTT causes a wide variety of debilitating symptoms and no cure currently exists. Mouse models bearing mutations in the Mecp2 gene recapitulate most physiological and behavioural RTT-related abnormalities. Stimulating neonatal environments (e.g. brief maternal separations or maternal low-dose corticosterone supplementation) reduces stress and fear responses at adulthood. The present study investigated whether impacting early in development the hypothalamic-pituitary-adrenal axis, by exposing Mecp2-308 mutant pups to a low dose of corticosterone (50 mg/ml, during the 1(st) week of life) may contrast RTT-related abnormalities in neuroendocrine regulation and behavioural adaptation at adulthood. In line with previous reports, when fully symptomatic, MeCP2-308 mice showed a reduction in the regular nocturnal hyperactivity in the home-cage and increased anxiety-like behaviours and plasma corticosterone (CORT) levels in response to restraint stress. An abnormal elevation in mRNA levels of mineralocorticoid receptors (MR) and BDNF gene was also evident in the hippocampus of fully symptomatic mutant mice. Neonatal CORT modulated MR gene expression and behavioral reactivity towards a novel object, also restoring wt-like levels of locomotor/exploratory behavior in mutant mice. Enhanced sensitivity to the neonatal treatment (in terms of increase in GR and MR mRNA levels), was also evident in the hippocampus of MeCP2-308 mice compared to wt littermates. Present results corroborate the hypothesis that pharmacological interventions targeting the glucocorticoid system may prove valid in contrasting at least some of the RTT-related symptoms and provide evidence that pharmacological interventions during critical early time windows can persistently improve the behavioural phenotype of RTT mice. Current data also support the emerging role played by Mecp2 in mediating the epigenetic programming induced by early life events and indicate that, in the absence of functional MeCP2, programming of the central nervous system in response to early environmental stimuli is abnormally regulated.
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2. Ghanizadeh A, Akhondzadeh S, Hormozi, Makarem A, Abotorabi M, Firoozabadi A. {{Glutathione-related Factors and Oxidative Stress in Autism, a Review}}. {Curr Med Chem};2012 (Jun 18)
Autism spectrum disorders are complex neuro-developmental disorders whose neurobiology is proposed to be associated with oxidative stress which is induced by reactive oxygen species. The process of oxidative stress can be a target for therapeutic interventions. In this study, we aimed to review the role of oxidative stress, plasma glutathione (GSH), and related factors as the potential sources of damage to the brain and the possible related factors which reduces oxidative stress. Methylation capacity, sulfates level, total glutathione level are decreased in autism. On the other hand, both oxidized glutathione and the ratio of oxidized to reduced glutathione are increased in autism. In addition, the activity of glutathione peroxidase, superoxide dismutase, and catalase as a part of antioxidative stress system are decreased. Current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing oxidative stress might be a potential treatment for autism.
3. Goldman S, Temudo T. {{Hand stereotypies distinguish Rett syndrome from autism disorder}}. {Mov Disord};2012 (Jun 18)
BACKGROUND: Rett syndrome (RTT) and autism disorder (AD) are 2 neurodevelopmental disorders of early life that share phenotypic features, one being hand stereotypies. Distinguishing RTT from AD often represents a challenge, and given their distinct long-term prognoses, this issue may have far-reaching implications. With the advances in genetic testing, the contribution of clinical manifestations in distinguishing RTT from AD has been overlooked. METHODS: A comparison of hand stereotypies in 20 children with RTT and 20 with AD was performed using detailed analyses of videotaped standardized observations. RESULTS: Striking differences are observed between RTT and AD children. In RTT, hand stereotypies are predominantly complex, continuous, localized to the body midline, and involving mouthing. Conversely, in AD children, hand stereotypies are simple, bilateral, intermittent, and often involving objects. CONCLUSIONS: These results provide important clinical signs useful to the differential diagnosis of RTT versus AD, especially when genetic testing for RTT is not an option. (c) 2012 Movement Disorder Society.
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4. Karim K, Cook L, O’Reilly M. {{Diagnosing autistic spectrum disorder in the age of austerity}}. {Child Care Health Dev};2012 (Jun 20)
BACKGROUND: Diagnosing autistic spectrum disorder is a challenge, typically involving myriad professionals. In the current climate we explore how diagnosis is managed in the real world by professionals. METHODS: Using semi-structured interviews we thematically analyse data from psychiatrists, paediatricians and educational psychologists. RESULTS: While there is some consistency across and within these groups there are also a number of variances, and several important issues are highlighted. These include the problem of time and resources, the issue of location for diagnosis, the value of diagnostic tools and schedules, the need for supporting information, the difficulty of multi-agency working, the relevance of a physical examination and the eventual diagnostic label. CONCLUSIONS: In the current economic climate and considering changes in guidelines there is a need to evaluate current service provision and enhance services. However, attention needs to be paid to the practical and realistic application of the suggested guidance.
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5. Kim M, Ceman S. {{Fragile X Mental Retardation Protein: Past, Present and Future}}. {Curr Protein Pept Sci};2012 (Jun 18)
We begin by reviewing the first characterization of fragile X syndrome, which ultimately led to cloning of the FMR1 gene. Discovery of the molecular basis of this disorder, including expansion of a trinucleotide repeat, gave insight not only into fragile X syndrome but also into the premutation syndromes. Features of fragile X syndrome are discussed including the patient phenotype down to the neuronal phenotype. The domain features of the fragile X mental retardation protein FMRP are described, as are the mRNAs bound by FMRP and the role of post- ranslational modifications as regulators of FMRP function. The relatively new role of FMRP in progenitor cells is reviewed, as is FMRP localization in cells and how FMRP is regulated by glutamatergic signaling in the brain. Understanding how metabotropic glutamate receptors impact FMRP has led to novel therapeutic approaches in treating this disorder.
6. Kirsten TB, Chaves-Kirsten GP, Chaible LM, Silva AC, Martins DO, Britto LR, Dagli ML, Torrao AS, Palermo-Neto J, Bernardi MM. {{Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide}}. {J Neurosci Res};2012 (Jun 20)
The aim of the present study was to evaluate the behavioral patterns associated with autism and the prevalence of these behaviors in males and females, to verify whether our model of lipopolysaccharide (LPS) administration represents an experimental model of autism. For this, we prenatally exposed Wistar rats to LPS (100 mug/kg, intraperitoneally, on gestational day 9.5), which mimics infection by gram-negative bacteria. Furthermore, because the exact mechanisms by which autism develops are still unknown, we investigated the neurological mechanisms that might underlie the behavioral alterations that were observed. Because we previously had demonstrated that prenatal LPS decreases striatal dopamine (DA) and metabolite levels, the striatal dopaminergic system (tyrosine hydroxylase [TH] and DA receptors D1a and D2) and glial cells (astrocytes and microglia) were analyzed by using immunohistochemistry, immunoblotting, and real-time PCR. Our results show that prenatal LPS exposure impaired communication (ultrasonic vocalizations) in male pups and learning and memory (T-maze spontaneous alternation) in male adults, as well as inducing repetitive/restricted behavior, but did not change social interactions in either infancy (play behavior) or adulthood in females. Moreover, although the expression of DA receptors was unchanged, the experimental animals exhibited reduced striatal TH levels, indicating that reduced DA synthesis impaired the striatal dopaminergic system. The expression of glial cell markers was not increased, which suggests that prenatal LPS did not induce permanent neuroinflammation in the striatum. Together with our previous finding of social impairments in males, the present findings demonstrate that prenatal LPS induced autism-like effects and also a hypoactivation of the dopaminergic system. (c) 2012 Wiley Periodicals, Inc.
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7. Suren P, Bakken IJ, Aase H, Chin R, Gunnes N, Lie KK, Magnus P, Reichborn-Kjennerud T, Schjolberg S, Oyen AS, Stoltenberg C. {{Autism Spectrum Disorder, ADHD, Epilepsy, and Cerebral Palsy in Norwegian Children}}. {Pediatrics};2012 (Jun 18)
BACKGROUND:Numerous studies have investigated the prevalence of neurologic and neurodevelopmental disorders individually, but few have examined them collectively, and there is uncertainty as to what extent they overlap.METHODS:The study has determined the proportions of children aged 0 to 11 years with diagnoses of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), epilepsy, and cerebral palsy (CP) in Norway. The data were obtained from the Norwegian Patient Register, which is nationwide and contains diagnoses assigned by Norwegian specialist health services (hospitals and outpatient clinics). The Norwegian Patient Register started collecting individual-level data in 2008, and the follow-up period for the study is years 2008 through 2010.RESULTS:For ASD, ADHD, and epilepsy, the proportions were highest in the oldest children. At age 11 years, the incidence was 0.7% for ASD, 2.9% for ADHD, and 0.9% for epilepsy. The cumulative incidence is likely to be higher because some cases diagnosed before 2008 were probably missed. For CP, the proportions were approximately 0.3% for age >/=5 years. There was considerable overlap between diagnoses. For all disorders, boys had a significantly increased risk. In school-age children (aged 6-11 years) the male/female ratio was 4.3 for ASD, 2.9 for ADHD, 1.2 for epilepsy, and 1.3 for CP.CONCLUSIONS:The findings demonstrate the significant burden of disease associated with neurologic and neurodevelopmental disorders in children and that this burden is disproportionately skewed toward boys.
