RESUMO
Autism spectrum disorder (ASD) is characterized by pervasive impairments in social communication along with repetitive or stereotyped behaviors. Although its distinctive etiology isn`t completely understood, genetic and environmental risk factors were incriminated. Being a flavonoid of high biomedical value, baicalin was recently verified as an emerging medicinal herb with numerous pharmacological activities. The objective of this study was to investigate the feasible effects of baicalin on valproic acid (VPA)-induced autism regarding its potential mitochondrial modulatory, antioxidant, and antiapoptotic effects. The present study was performed using a rodent model of autism by exposing rat fetuses to VPA on the 12.5th day of gestation. Ten male Wistar rats that were born from control pregnant females were considered as group I (control group). Twenty male Wistar rats that were born from prenatal VPA- treated females were further divided into two groups: Group II (VPA- induced ASD) and group III (VPA + Baicalin). Postnatal baicalin promoted postnatal growth and maturation. In addition, it improved motor development and ameliorated repetitive behavior as well as social deficits in prenatally exposed VPA rats. Moreover, baicalin enhanced neuronal mitochondrial functions as evidenced by elevation of mitochondrial adenosine triphosphate (ATP) level and promotion of mitofusin-2 expression. Furthermore, baicalin elevated sirtuin-1 (SIRT1) level in VPA rats' brain tissues and restored the antioxidant defense mechanisms. Besides, it abrogated the neuronal histopathological changes in the brain tissues. Based on the data herein, baicalin may provide a promising pre-clinical therapeutic line in ASD as a mitochondrial function modulator, antioxidant and anti-apoptotic agent.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Efeitos Tardios da Exposição Pré-Natal , Animais , Antioxidantes , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/patologia , Comportamento Animal , Modelos Animais de Doenças , Feminino , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Wistar , Roedores , Sirtuína 1 , Ácido ValproicoRESUMO
Autism Spectrum Disorders (ASD) are characterised by deficits in social interactions and repetitive behaviours. Multiple ASD-associated mutations have been identified in the Shank family of proteins that play a critical role in the structure and plasticity of glutamatergic synapses, leading to impaired synapse function and the presentation of ASD-associated behavioural deficits in mice. Shank proteins are highly regulated by zinc, where zinc binds the Shank SAM domain to drive synaptic protein recruitment and synaptic maturation. Here we have examined the influence of maternal dietary zinc supplementation during pregnancy and lactation on the development of ASD-associated behavioural and synaptic changes in the offspring Shank3 knockout (Shank3-/-) mice. Behavioural and electrophysiological experiments were performed in juvenile and adult Shank3-/- and wildtype littermate control mice born from mothers fed control (30 ppm, ppm) or supplemented (150 ppm) dietary zinc. We observed that the supplemented maternal zinc diet prevented ASD-associated deficits in social interaction and normalised anxiety behaviours in Shank3-/- offspring mice. These effects were maintained into adulthood. Repetitive grooming was also prevented in adult Shank3-/- offspring mice. At the synaptic level, maternal zinc supplementation altered postsynaptic NMDA receptor-mediated currents and presynaptic function at glutamatergic synapses onto medium spiny neurons in the cortico-striatal pathway of the Shank3-/- offspring mice. These data show that increased maternal dietary zinc during pregnancy and lactation can alter the development of ASD-associated changes at the synaptic and the behavioural levels, and that zinc supplementation from the beginning of brain development can prevent ASD-associated deficits in Shank3-/- mice long term.
Assuntos
Transtorno Autístico/patologia , Comportamento Animal , Suplementos Nutricionais , Proteínas dos Microfilamentos/deficiência , Proteínas do Tecido Nervoso/deficiência , Sinapses/patologia , Zinco/farmacologia , Animais , Ansiedade/patologia , Encéfalo/metabolismo , Feminino , Glutamatos/metabolismo , Asseio Animal , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Gravidez , Receptores de AMPA/metabolismo , Comportamento Social , Espectrofotometria Atômica , Sinapses/efeitos dos fármacosRESUMO
Autism is a developmental disorder that affects communication and behavior. Although autism can be diagnosed at any age, it is said to be a "developmental disorder" because symptoms generally appear in the first 2 years of life. The primary cause of autism is still not clear and therapy is currently restricted to controlling behavioral abnormalities. However, emerging studies have shown a link between mitochondrial dysfunction and autism. Dietary supplements that promote mitochondrial biogenesis and inhibit the production of oxidative stress have been used to treat autism patients. Dietary adjustments in treating autism is a novel approach to suppress autistic symptoms. Supplementation with antioxidants has been found to not only inhibit cognitive decline but also improve behavioral symptoms in autism. Dietary supplements fortified with vitamins should only be given under the supervision of a physician. A wide range of nutraceuticals are under clinical trials to understand whether they physiologically target mitochondrial pathways and improve the quality of life in autism.
Assuntos
Transtorno Autístico/dietoterapia , Dietoterapia , Proteínas Alimentares/uso terapêutico , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Suplementos Nutricionais , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Qualidade de VidaRESUMO
BACKGROUND: Autism Spectrum Disorder (ASD) is a complex disorder with heterogeneous etiology and wide clinical severity which supports the needs of recognizing biological and clinical features in patient subsets. The present study aimed to understand possible associations between the hair levels of metals and essential elements and some specific features of ASD measured by the Autism Diagnostic Observation Schedule (ADOS) that represents the gold-standard instrument to objectively confirm ASD diagnosis. METHODS: A cross-sectional study was performed in the province of Catania (Sicily, South Italy). Forty-eight subjects with ASD (70.8% male), aged from 2 to 17 years were studied. Metals (Li, Be, Al, Ni, As, Mo, Cd, Hg, U, Pb) and essential trace elements (Cr, Co, Mn, Zn, Cu, Se) were quantified in hair by inductively coupled plasma mass spectrometry analysis. Participants were characterized by measuring the severity of autism symptoms and cognitive levels. RESULTS: A significant and positive correlation was found between hair metal burden (lead, aluminum, arsenic and cadmium levels) and severity of ASD symptoms (social communication deficits and repetitive, restrictive behaviors). Hair zinc level were inversely related with age while there was a negative, significant association between hair zinc level and severity of autistic symptoms (defective functional play and creativity and increase of stereotyped behavior). Lead, molybdenum and manganese hair levels were inversely correlated with cognitive level (full intelligence quotient) in ASD individuals. CONCLUSIONS: The present study suggests the importance to combine metallomics analysis with pertinent disease features in ASD to identify potential environmental risk factors on an individual level possibly in the early developmental period.
Assuntos
Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Oligoelementos/análise , Adolescente , Arsênio/análise , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/patologia , Cádmio/análise , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Itália , Masculino , Manganês/análise , Mercúrio/análise , Metais , Molibdênio/análise , Selênio/análiseRESUMO
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disease characterized by defect in verbal and nonverbal communications. As, the cerebellum has the greatest number of neurons and synapses in the central nervous system so, the cerebellum has emerged as one of the target brain areas affected in autism. The aim of this work was to study the biochemical, immunohistochemical and ultrastructural characteristics of autism and the possible neuroprotective role of grape seed extract. In this study 28 male pups were divided into Control groups; Group I (saline), Group II (GSE 400â¯mg/kg), Group III (VPA 500â¯mg/kg) and Group IV (VPA and GSE). Cerebellar hemispheres were dissected out and prepared to determine the oxidative stress markers, histological, immunohistochemical and morphometric study were done. A significant elevation in oxidative stress markers in off spring of VPA treated rats in comparison to control group was detected. A significant decrease in the Purkinje cell count and nuclear size were observed. Numerous shrunken cells with hyperchromatic nuclei and ultrastructural degeneration of cytoplasmic organelles were detected. A significant rise in the area percentage of GFAP-positive immune stained cells in comparison to that of the control groups was seen. Strikingly, GSE revealed significant improvement in the oxidative stress markers and then the histological and morphometric picture of the cerebellum. GSE has neuroprotective effect on the cerebellum of VPA treated rats through its potent antioxidant effect.
Assuntos
Transtorno Autístico , Córtex Cerebelar , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Sementes/química , Ácido Valproico/efeitos adversos , Vitis/química , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Transtorno Autístico/prevenção & controle , Córtex Cerebelar/metabolismo , Córtex Cerebelar/patologia , Modelos Animais de Doenças , Feminino , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Ratos , Ácido Valproico/farmacologiaRESUMO
Autistic spectrum disorders (ASDs) are neurodevelopmental disorders for which genetic components have been well defined. However, specific gene deregulations related to synapse function in the autistic brain have not been as extensively described. Based on a candidate genes approach, we present in this study the expression data of 4 transcripts of interest (BDNF, CAMK2a, NR-CAM and RIMS1) located at the synapse in two regions of interest in the context of the ASDs; the lobule VI of cerebellum and the Brodmann area 46. We have also genotyped in our cohort the coding single nucleotide polymorphism rs6265, located in the BDNF gene. After correction for age and sex, whereas no change was observed in the lobule VI between controls and autistic patients, we found a significant increase of BDNF expression level in the BA46 from autistic patients. No significant interaction between the rs6265 genotype and autism was observed for the BDNF expression. However, "A" allele carriers are more likely to have increased BDNF levels. Finally, we found a significant positive correlation between BDNF and RIMS1 expression levels. Our data suggest that these two molecules which are involved in cell signalling at the synapse, might have coordinated expressions and, that BDNF regulation in the brain has to be investigated further in the context of ASDs.
Assuntos
Transtorno Autístico/patologia , Fator Neurotrófico Derivado do Encéfalo/genética , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/metabolismo , Adolescente , Adulto , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Criança , Pré-Escolar , Diagnóstico , Feminino , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Genótipo , Humanos , Microdissecção e Captura a Laser , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Adulto JovemRESUMO
BACKGROUND: Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism. METHODS: The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level. RESULTS: A significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA. CONCLUSION: Both ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.
Assuntos
Transtorno Autístico/tratamento farmacológico , Colesterol/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Vitamina B 12/metabolismo , Animais , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Hidrólise/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fosfolipases A2/metabolismo , Fosfolipídeos/metabolismo , Propionatos/administração & dosagem , RatosRESUMO
The present study was undertaken to elucidate the effect of alpha-linolenic acid (ALA, 18:3, ω-3) and gamma-linolenic acid (GLA, 18:3, ω-6) on experimental autism features induced by early prenatal exposure to valproic acid (VPA) in albino wistar pups. The pups were scrutinized on the accounts of behavioral, biochemical, and inflammatory markers, and the results suggested that the GLA can impart significant protection in comparison to ALA against VPA-induced autism features. When scrutinized histopathologically, the cerebellum of the GLA-treated animals was evident for more marked protection toward neuronal degeneration and neuronal loss in comparison to ALA. Concomitant administration of ALA and GLA with VPA demonstrated a marked cutdown in the Pgp 9.5 expression with GLA having more pronounced effect. Henceforth, it can be concluded that ALA and GLA can impart favorable protection against the VPA-induced autism-like features with GLA having pronounced effect.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Transtorno Autístico/prevenção & controle , Suplementos Nutricionais , Modelos Animais de Doenças , Fármacos Neuroprotetores/uso terapêutico , Ácido alfa-Linolênico/uso terapêutico , Ácido gama-Linolênico/uso terapêutico , Animais , Animais Recém-Nascidos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/toxicidade , Antimaníacos/toxicidade , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/imunologia , Transtorno Autístico/patologia , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Suplementos Nutricionais/efeitos adversos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/imunologia , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Ubiquitina Tiolesterase/metabolismo , Ácido Valproico/toxicidade , Ácido alfa-Linolênico/efeitos adversos , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/metabolismo , Ácido gama-Linolênico/efeitos adversos , Ácido gama-Linolênico/sangue , Ácido gama-Linolênico/metabolismoRESUMO
Multiple factors such as genetic and extraneous causes (drugs, toxins, adverse psychological events) contribute to neuro-psychiatric conditions. In a subgroup of these disorders, systemic folate deficiency has been associated with macrocytic anemia and neuropsychiatric phenotypes. In some of these, despite normal systemic levels, folate transport to the brain is impaired in the so-called cerebral folate deficiency (CFD) syndromes presenting as developmental and psychiatric disorders. These include infantile-onset CFD syndrome, infantile autism with or without neurologic deficits, a spastic-ataxic syndrome and intractable epilepsy in young children expanding to refractory schizophrenia in adolescents, and finally treatment-resistant major depression in adults. Folate receptor alpha (FRα) autoimmunity with low CSF N(5)-methyl-tetrahydrofolate (MTHF) underlies most CFD syndromes, whereas FRα gene abnormalities and mitochondrial gene defects are rarely found. The age at which FRα antibodies of the blocking type emerge, determines the clinical phenotype. Infantile CFD syndrome and autism with neurological deficits tend to be characterized by elevated FRα antibody titers and low CSF MTHF. In contrast, in infantile autism and intractable schizophrenia, abnormal behavioral signs and symptoms may wax and wane with fluctuating FRα antibody titers over time accompanied by cycling changes in CSF folate, tetrahydrobiopterin (BH4) and neurotransmitter metabolites ranging between low and normal levels. We propose a hypothetical model explaining the pathogenesis of schizophrenia. Based on findings from clinical, genetic, spinal fluid and MRI spectroscopic studies, we discuss the neurochemical changes associated with these disorders, metabolic and regulatory pathways, synthesis and catabolism of neurotransmitters, and the impact of oxidative stress on the pathogenesis of these conditions. A diagnostic algorithm and therapeutic regimens using high dose folinic acid, corticosteroids and milk-free diet is presented which has proven to be beneficial in providing adequate folate to the brain and decreasing the FRα autoantibody titer in those positive for the antibody.
Assuntos
Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/metabolismo , Leucovorina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Adolescente , Adulto , Transtorno Autístico/patologia , Feminino , Humanos , Masculino , Esquizofrenia/patologiaRESUMO
Folates are essential in the intermediary metabolism of amino acids, synthesis of nucleotides and for maintaining methylation reactions. They are also linked to the production of neurotransmitters through GTP needed for the synthesis of tetrahydrobiopterin. During pregnancy, folate is needed for fetal development. Folate deficiency during this period has been linked to increased risk of neural tube defects. Disturbances of folate metabolism due to genetic abnormalities or the presence of autoantibodies to folate receptor alpha (FRα) can impair physiologic processes dependent on folate, resulting in a variety of developmental disorders including cerebral folate deficiency syndrome and autism spectrum disorders. Overall, adequate folate status has proven to be important during pregnancy as well as neurological development and functioning in neonates and children. Treatment with pharmacologic doses of folinic acid has led to reversal of some symptoms in many children diagnosed with cerebral folate deficiency syndrome and autism, especially in those positive for autoantibodies to FRα. Thus, as the brain continues to develop throughout fetal and infant life, it can be affected and become dysfunctional due to a defective folate transport contributing to folate deficiency. Treatment and prevention of these disorders can be achieved by identification of those at risk and supplementation with folinic acid.
Assuntos
Transtorno Autístico , Deficiência de Ácido Fólico , Ácido Fólico , Defeitos do Tubo Neural , Animais , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Autoanticorpos/metabolismo , Transporte Biológico Ativo/genética , Feminino , Receptor 1 de Folato/antagonistas & inibidores , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Deficiência de Ácido Fólico/genética , Deficiência de Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/patologia , Humanos , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/patologia , GravidezRESUMO
Introducción. La teoría de la mente se define como la capacidad para predecir, comprender y actuar frente a la conducta de otras personas, sus conocimientos, sus intenciones, sus emociones y sus creencias. Se plantea como una alternativa viable para establecer un programa adaptado a las características de los niños diagnosticados con trastorno del espectro autista. Casos clínicos. Se describe el efecto de un programa piloto de desarrollo cognitivo teoría de la mente en las habilidades emocionales de tres niños con trastorno del espectro autista. Caso 1: niño de 9 años, con escasa identificación y expresión emocional, así como dificultades para mantener conversaciones fluidas y coherentes. Caso 2: niño de 10 años, con lenguaje mecánico, poco fluido, y dificultades para iniciar y mantener una conversación. Caso 3: niña de 8 años que presenta déficits en las conductas comunicativas no verbales usadas en la interacción social y dificultades para adaptarse a situaciones no cotidianas. En los tres casos se presenta mejoría de las capacidades emocionales posterior a la implementación del programa; además, los padres, docentes o terapeutas percibieron cambios positivos en las habilidades adaptativas de los niños. Conclusiones. Los aspectos metodológicos y estructurales del programa de desarrollo cognitivo fueron adecuados para los niños con autismo participantes de la investigación. Debido al carácter preliminar del estudio, se sugiere para futuras investigaciones una muestra mayor y un diseño doble ciego con aleatorización caso/control que permitan la generalización de los resultados (AU)
Introduction. Theory of mind is defined as the capacity to predict, understand and act when faced with other peoples behaviour, their knowledge, their intentions, their emotions and their beliefs. It is proposed as a feasible alternative for establishing a programme adapted to the characteristics of children diagnosed with autism spectrum disorder. Case reports. The effect of a theory of mind cognitive development pilot programme on the emotional skills of three children with autism spectrum disorder is reported. Case 1: 9-year-old boy, with scarce emotional identification and expression, as well as difficulties to hold fluent and coherent conversations. Case 2: 10-year-old boy, with mechanical, not very fluent language, and difficulties to start and maintain a conversation. Case 3: 8-year-old girl who presents deficits in the non-verbal communicative behaviours used in social interaction and difficulties to adapt to situations other than everyday ones. In the three cases there is an improvement in the emotional capacities following implementation of the programme; moreover, their parents, teachers or therapists perceived positive changes in the childrens adaptive skills. Conclusions. The methodological and structural aspects of the cognitive development programme were well-suited to the children with autism who took part in the research study. Due to the preliminary nature of this study, it is suggested that future research should utilise a larger sample and a double-blind design with randomised case-controls that allow the findings to be generalised (AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Terapia Cognitivo-Comportamental/métodos , Transtornos Cognitivos/complicações , Transtornos Cognitivos/diagnóstico , Psicofisiologia , Terapias Mente-Corpo/métodos , Teoria da Mente , Teoria da Mente/ética , Transtorno Autístico/psicologia , Desempenho de Papéis , Projetos Piloto , Sintomas Afetivos/epidemiologia , Sintomas Afetivos/prevenção & controle , Competência em Informação , Teoria da Mente/classificação , Teoria da Mente/fisiologia , Transtorno Autístico/patologiaRESUMO
In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC.
Assuntos
Transtorno Autístico/complicações , Transtorno Autístico/patologia , Córtex Cerebral/patologia , Lateralidade Funcional/fisiologia , Transtornos do Desenvolvimento da Linguagem/etiologia , Estimulação Acústica , Adolescente , Adulto , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Percepção Espacial , Estatística como Assunto , Adulto JovemRESUMO
Autism is a severe neurodevelopmental disorder with a population prevalence of 1 in 68, and dramatically increasing. While no single pharmacologic intervention has successfully targeted the core symptoms of autism, emerging evidence suggests that postnatal environmental manipulations may offer greater therapeutic efficacy. Massage therapy, or tactile stimulation (TS), early in life has repeatedly been shown to be an effective, low-cost, therapeutic approach in ameliorating the cognitive, social, and emotional symptoms of autism. While early TS treatment attenuates many of the behavioral aberrations among children with autism, the neuroanatomical correlates driving such changes are unknown. The present study assessed the therapeutic effects of early TS treatment on behavior and neuroanatomy using the valproic acid (VPA) rodent model of autism. Rats were prenatally exposed to VPA on gestational day 12.5 and received TS shortly following birth. Whereas TS reversed almost all the VPA-induced alterations in neuroanatomy, it failed to do so behaviorally. The TS VPA animals, when compared to VPA animals, did not exhibit altered or improved behavior in the delayed non-match-to-sample T-maze, Whishaw tray reaching, activity box, or elevated plus maze tasks. Anatomically, however, there were significant increases in dendritic branching and spine density in the medial prefrontal cortex, orbital frontal cortex, and amygdala in VPA animals following early TS treatment, suggesting a complete reversal or remediation of the VPA-induced effects in these regions. The results suggest that postnatal TS, during a critical period in development, acts as a powerful reorganization tool that can ameliorate the neuroanatomical consequences of prenatal VPA exposure.
Assuntos
Transtorno Autístico/patologia , Transtorno Autístico/terapia , Plasticidade Neuronal , Tato , Ácido Valproico/toxicidade , Tonsila do Cerebelo/patologia , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/psicologia , Comportamento Animal , Dendritos/patologia , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Feminino , Lobo Frontal/patologia , Masculino , Aprendizagem em Labirinto , Atividade Motora , Córtex Pré-Frontal/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Ratos Long-Evans , Comportamento SocialRESUMO
BACKGROUND: An enhanced plasticity is suspected to play a role in various microstructural alterations, as well as in regional cortical reallocations observed in autism. Combined with multiple indications of enhanced perceptual functioning in autism, and indications of atypical motor functioning, enhanced plasticity predicts a superior variability in functional cortical allocation, predominant in perceptual and motor regions. METHOD: To test this prediction, we scanned 23 autistics and 22 typical participants matched on age, FSIQ, Raven percentile scores and handedness during a visuo-motor imitation task. For each participant, the coordinates of the strongest task-related activation peak were extracted in the primary (Brodmann area 4) and supplementary (BA 6) motor cortex, the visuomotor superior parietal cortex (BA 7), and the primary (BA 17) and associative (BAs 18 + 19) visual areas. Mean signal changes for each ROI in both hemispheres, and the number of voxels composing the strongest activation cluster were individually extracted to compare intensity and size of the signal between groups. For each ROI, in each hemisphere, and for every participant, the distance from their respective group average was used as a variable of interest to determine group differences in localization variability using repeated measures ANOVAs. Between-group comparison of whole-brain activation was also performed. RESULTS: Both groups displayed a higher mean variability in the localization of activations in the associative areas compared to the primary visual or motor areas. However, despite this shared increased variability in associative cortices, a direct between-group comparison of the individual variability in localization of the activation revealed a significantly greater variability in the autistic group than in the typical group in the left visuo-motor superior parietal cortex (BA 7) and in the left associative visual areas (BAs 18 + 19). CONCLUSION: Different and possibly unique strategies are used by each autistic individual. That enhanced variability in localization of activations in the autistic group is found in regions typically more variable in non-autistics raises the possibility that autism involves an enhancement and/or an alteration of typical plasticity mechanisms. The current study also highlights the necessity to verify, in fMRI studies involving autistic people, that hypoactivation at the group level does not result from each individual successfully completing a task using a unique brain allocation, even by comparison to his own group.
Assuntos
Transtorno Autístico/patologia , Córtex Cerebral/patologia , Atividade Motora/fisiologia , Percepção Visual/fisiologia , Adolescente , Adulto , Anoctaminas , Transtorno Autístico/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/irrigação sanguínea , Canais de Cloreto , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imaginação , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
With the development of autism therapy, acupuncture, an alternative therapy, is becoming popular for autism children. There have been many papers found about the treatment of autism by acupuncture therapy so far. In the present review, the authors briefly introduce the theoretical basis of autism in traditional Chinese medicine and the application history, and sum up the acupoint prescriptions, effectiveness as well as the assessment tools of acupuncture therapy for autism. It is suggested that acupuncture therapy is a relatively effective therapy for autism children. It has positive roles in improving autistic syndromes without any side-effects, especially in improving language development, daily-life self-care, and social communications. The underlying mechanism of this therapy may be explained by acupuncture intervention induced favorable changes of neurochemistry, cerebral blood flow, and cerebral functional activities. Although there are lots of questions to be answered about acupuncture treatment of autism, we hold a positive opinion that this therapy might be a green effective therapy for autistic children in the future.
Assuntos
Terapia por Acupuntura/métodos , Transtorno Autístico/terapia , Pontos de Acupuntura , Transtorno Autístico/patologia , Transtorno Autístico/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Criança , Humanos , Resultado do TratamentoRESUMO
We present a case of scurvy in a 6-year-old boy with autism and an unbalanced diet. The patient was admitted with difficulties in walking. Magnetic resonance imaging findings of the thigh showed diffuse signal abnormality in the bone marrow, periosteum, and the femoral muscle. A biopsy specimen of the femur showed hematoma, proliferative fibroblasts, and few collagen fibers, which suggested a deficiency of vitamin C. Although recurrent periosteal hematoma may be suggestive of scurvy, this finding was subtle in the current case. It is important to be aware of this rare disease because it is easily cured with vitamin C supplementation.
Assuntos
Transtorno Autístico/complicações , Transtorno Autístico/patologia , Imageamento por Ressonância Magnética , Escorbuto/etiologia , Escorbuto/patologia , Ácido Ascórbico/metabolismo , Ácido Ascórbico/uso terapêutico , Criança , Fêmur/anormalidades , Hematoma/etiologia , Hematoma/patologia , Humanos , Masculino , Prognóstico , Coxa da Perna/anormalidadesRESUMO
This functional magnetic resonance imaging study compared the neural activation patterns of 18 high-functioning individuals with autism and 18 IQ-matched neurotypical control participants as they learned to perform a social judgment task. Participants learned to identify liars among pairs of computer-animated avatars uttering the same sentence but with different facial and vocal expressions, namely those that have previously been associated with lying versus truth-telling. Despite showing a behavioral learning effect similar to the control group, the autism group did not show the same pattern of decreased activation in cortical association areas as they learned the task. Furthermore, the autism group showed a significantly smaller increase in interregion synchronization of activation (functional connectivity) with learning than did the control group. Finally, the autism group had decreased structural connectivity as measured by corpus callosum size, and this measure was reliably related to functional connectivity measures. The findings suggest that cortical underconnectivity in autism may constrain the ability of the brain to rapidly adapt during learning.
Assuntos
Aprendizagem por Associação/fisiologia , Transtorno Autístico/patologia , Transtorno Autístico/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Comportamento Social , Estimulação Acústica , Adolescente , Adulto , Análise de Variância , Estudos de Casos e Controles , Córtex Cerebral/irrigação sanguínea , Corpo Caloso/irrigação sanguínea , Corpo Caloso/patologia , Corpo Caloso/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiopatologia , Oxigênio/sangue , Tempo de Reação , Adulto JovemRESUMO
BACKGROUND: Subjects with autism suffer from impairments of social interaction, deviations in language usage, as well as restricted and stereotyped patterns of behavior. These characteristics are found irrespective of age, IQ, and gender of affected subjects. However, brain changes due to age, IQ, and gender might pose potential confounds in autism neuroimaging analyses. METHODS: To investigate gray matter differences in autism that are not related to these potential confounds, we performed a voxel-based morphometry analysis in 52 affected children and adolescents and 52 matched control subjects. RESULTS: We observed diminished gray matter in a region of the hypothalamus, which synthesizes the behaviorally relevant hormones oxytocin and arginine vasopressin. CONCLUSIONS: This finding provides support for further investigations of the theory of abnormal functioning of this hormonal system in autism and potentially for experimental therapeutic approaches with oxytocin and related neuropeptides.
Assuntos
Transtorno Autístico/patologia , Hipotálamo/patologia , Fibras Nervosas Amielínicas/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Hormônios Neuro-Hipofisários/fisiologia , Adulto JovemRESUMO
The formation and manipulation of mental images represents a key ability for successfully solving visuospatial tasks like Wechsler's Block Design or visual reasoning problems, tasks where autistics perform at higher levels than predicted by their Wechsler IQ. Visual imagery can be used to compare two mental images, allowing judgment of their relative properties. To examine higher visual processes in autism, and their possible role in explaining autistic visuospatial peaks, we carried out two mental imagery experiments in 23 autistic and 14 age and IQ matched, non-autistic adolescents and adults. Among autistics, 11 had significantly higher Block Design scores than predicted by their IQ. Experiment 1 involved imagining a letter inside a circle, followed by a decision concerning which of two highlighted portions of the circle would contain the greater proportion of the letter. Experiment 2 involved four classic mental rotation tasks utilizing two- and three-dimensional geometric figures, hands and letters. Autistics were more accurate in the formation and comparison of mental images than non-autistics. Autistics with a Block Design peak outperformed other participants in both speed and accuracy of mental rotation. Also, Performance IQ and Block Design scores were better predictors of mental rotation accuracy in autistic compared to non-autistic participants. The ability to form, access and manipulate visual mental representations may be more developed in autistics. We propose two complementary mechanisms to explain these processing advantages: (1) a global advantage in perceptual processing, discussed in the framework of the enhanced perceptual functioning model, and (2) particular strengths in veridical mapping, the ability to efficiently detect isomorphisms among entities and then to use these mappings to process stimulus characteristics, thereby facilitating judgments about their differences.
Assuntos
Transtorno Autístico/patologia , Transtorno Autístico/fisiopatologia , Imaginação/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Distribuição Aleatória , Tempo de Reação/fisiologia , Rotação , Estatística como Assunto , Escalas de Wechsler , Adulto JovemRESUMO
Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG activation, which provides crucial information about functional integrity of connections between brain areas involved in cross-sensory processing in both disorders. Thirteen high functioning adult males with ASD, 13 high functioning adult males with schizophrenia, and 16 healthy adult males participated in the study. No differences in neither auditory nor cross-sensory P50 suppression were found between healthy controls and individuals with ASD. In schizophrenia, attenuated P50 responses to the first auditory stimulus indicated early auditory processing deficits. These results are in accordance with the notion that filtering deficits may be secondary to earlier sensory dysfunction. Also, atypical cross-sensory suppression was found, which implies that the cognitive impairments seen in schizophrenia may be due to deficits in the integrity of connections between brain areas involved in low-level cross-sensory processing.