- Reduced CD4 T Lymphocytes in Lymph Nodes of the Mouse Model of Autism Induced by Valproic Acid. [Journal Article]
- NNeuroimmunomodulation 2018 Aug 17; :1-5
- Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal m...
Considering the potential role of lymphocytes in the pathophysiology of autism spectrum disorder (ASD), we aimed to evaluate possible alterations of T cell pools in the lymphoid organs of an animal model of autism induced by valproic acid (VPA). Pregnant Swiss mice received a single intraperitoneal injection of 600 mg/kg of VPA (VPA group) or saline (control group) on day 11 of gestation. Male offspring were euthanized on postnatal day 60 for removal of thy-muses, spleens, and a pool of inguinal, axillary and brachial lymph nodes. Cellularity was evaluated, and flow cytometry analysis was performed on cell suspensions incubated with the mouse antibodies anti-CD3-FITC, anti-CD4-PE, and anti-CD8-PE-Cy7. We observed that the prenatal exposure to VPA induced a reduction in the numbers of CD3+CD4+ T cells in their lymph nodes when compared to the control animals. This was specific since it was not seen in the thymus or spleen. The consistent decrease in the number of CD4+ T cells in subcutaneous lymph nodes of mice from the animal model of autism may be related to the allergic symptoms frequently observed in ASD. Further research is necessary to characterize the immunological patterns in ASD and the connection with the pathophysiology of this disorder.
- Na+ , K+ -ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells. [Journal Article]
- ARAutism Res 2018 Aug 18
- Na+ , K+ -ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of n...
Na+ , K+ -ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Research 2018. © 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.
- Acquisition of Verb Meaning From Syntactic Distribution in Preschoolers With Autism Spectrum Disorder. [Journal Article]
- LSLang Speech Hear Serv Sch 2018 Aug 14; 49(3S):668-680
- CONCLUSIONS: This finding replicates and extends prior work on verb learning in children with ASD by demonstrating that they can attend to a novel verb's syntactic distribution absent relevant visual or social context, and they can use this information to assign the novel verb an appropriate meaning. We discuss points for future research, including examining individual differences that may impact success and contrasting social and nonsocial word-learning tasks directly.
- Distributional Cues to Language Learning in Children With Intellectual Disabilities. [Journal Article]
- LSLang Speech Hear Serv Sch 2018 Aug 14; 49(3S):653-667
- CONCLUSIONS: Critical gaps in the literature are highlighted. Research in this area is especially limited for Down syndrome and fragile X syndrome. Future directions for taking learning theories into account in interventions for children with intellectual disability are discussed, with a focus on the importance of language input.
- A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). [Journal Article]
- AJAm J Med Genet C Semin Med Genet 2018 Aug 16
- Tuberous sclerosis complex (TSC) is associated with a wide range of behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial difficulties, which are often underdiagnosed ...
Tuberous sclerosis complex (TSC) is associated with a wide range of behavioral, psychiatric, intellectual, academic, neuropsychological, and psychosocial difficulties, which are often underdiagnosed and undertreated. Here, we present a clinical update on TSC-associated neuropsychiatric disorders, abbreviated as "TAND," to guide screening, diagnosis, and treatment in practice. The review is aimed at clinical geneticists, genetic counselors, pediatricians, and all generalists involved in the assessment and treatment of children, adolescents and adults with TSC, and related disorders. The review starts with a summary of the construct and levels of TAND, before presenting up-to-date information about each level of investigation. The review concludes with a synopsis of current and future TAND research.
- Correction to: Outcomes of a Behavioral Intervention for Sleep Disturbances in Children with Autism Spectrum Disorder. [Published Erratum]
- JAJ Autism Dev Disord 2018 Aug 16
- The original version of this article unfortunately contained errors. The errors induced during the production process are corrected. The correct keywords, figures and tables are given below.
The original version of this article unfortunately contained errors. The errors induced during the production process are corrected. The correct keywords, figures and tables are given below.
- Dysregulation of Parvalbumin Expression in the Cntnap2-/- Mouse Model of Autism Spectrum Disorder. [Journal Article]
- FMFront Mol Neurosci 2018; 11:262
- Due to the complex and heterogeneous etiology of autism spectrum disorder (ASD), identification of convergent pathways and/or common molecular endpoints in the pathophysiological processes of ASD dev...
Due to the complex and heterogeneous etiology of autism spectrum disorder (ASD), identification of convergent pathways and/or common molecular endpoints in the pathophysiological processes of ASD development are highly needed in order to facilitate treatment approaches targeted at the core symptoms. We recently reported on decreased expression of the Ca2+-binding protein parvalbumin (PV) in three well-characterized ASD mouse models, Shank1-/-, Shank3B-/- and in utero VPA-exposed mice. Moreover, PV-deficient mice (PV+/- and PV-/-) were found to show behavioral impairments and neuroanatomical changes closely resembling those frequently found in human ASD individuals. Here, we combined a stereology-based approach with molecular biology methods to assess changes in the subpopulation of PV-expressing (Pvalb) interneurons in the recently characterized contactin-associated protein-like 2 (Cntnap2-/-) knockout mouse model of ASD. The CNTNAP2 gene codes for a synaptic cell adhesion molecule involved in neurodevelopmental processes; mutations affecting the human CNTNAP2 locus are associated with human ASD core symptoms, in particular speech and language problems. We demonstrate that in Cntnap2-/- mice, no loss of Pvalb neurons is evident in ASD-associated brain regions including the striatum, somatosensory cortex (SSC) and medial prefrontal cortex (mPFC), shown by the unaltered number of Pvalb neurons ensheathed by VVA-positive perineuronal nets. However, the number of PV-immunoreactive (PV+) neurons and also PV protein levels were decreased in the striatum of Cntnap2-/- mice indicating that PV expression levels in some striatal Pvalb neurons dropped below the detection limit, yet without a loss of Pvalb neurons. No changes in PV+ neuron numbers were detected in the cortical regions investigated and also cortical PV expression levels were unaltered. Considering that Cntnap2 shows high expression levels in the striatum during human and mouse embryonic development and that the cortico-striato-thalamic circuitry is important for speech and language development, alterations in striatal PV expression and associated (homeostatic) adaptations are likely to play an important role in Cntnap2-/- mice and, assumingly, in human ASD patients with known Cntnap2 mutations.
- Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study. [Journal Article]
- MPMol Psychiatry 2018 Aug 16
- Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide associati...
Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals from the general population (n = 30,000) were obtained. After quality control, the sample consisted of 6024 cases with an incidence of suicide attempt and 44,240 controls with no record of a suicide attempt. Suggestive associations between SNPs, rs6880062 (p-value: 5.4 × 10-8) and rs6880461 (p-value: 9.5 × 10-8), and suicide attempt were identified when adjusting for socio-demographics. Adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 (p-value: 2.8 × 10-8), rs4810824 (p-value: 3.5 × 10-8), and rs6019297 (p-value: 4.7 × 108). Sub-group analysis of cases with affective disorders revealed SNPs associated with suicide attempts when compared to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9-6.3%] of the variation in suicide attempt. Controlling for mental disorders reduced the heritability to 1.9% [CI-95: 0.3-3.5%]. Affective and autism spectrum disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9-9.3%] and 9.6% [CI-95: 1.1-18.1%], respectively. Using the largest sample to date, we identified significant SNP associations with suicide attempts and support for a genetic transmission of suicide attempt, which might not solely be explained by mental disorders.
- Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins. [Journal Article]
- SciScience 2018 Aug 17; 361(6403):709-712
- Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functiona...
Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.
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- Grandparents' roles and psychological well-being in the elderly: a correlational study in families with an autistic child. [Journal Article]
- ECEnferm Clin 2018 Feb - Jun; 28 Suppl 1:304-309
- CONCLUSIONS: The test results indicate a significant correlation between the roles of grandparents and their psychological well-being. The greater the role played by grandparents, the higher psychological well-being they experienced, and vice versa. Grandparents play an important role in families where there is a child with autism; they take care of the child when the parents are not at home, help with the cost of therapy, and take care of them when sick.