Synaptogenesis is a critical process in the establishment of neuronal connectivity during brain development. The key step is to transduce external stimuli into the internal signaling cascades. Cell adhesion molecules and scaffold proteins facilitate the transduction to achieve optimal connectivity through PDZ domain mediated interaction. FRMPD2, a product of a human-specific multi-copy gene with three PDZ domains, has been shown to localize to the tight junctions in epithelial cells, suggesting a role in inter-cellular interaction. Although the correlation between neurodevelopmental disorders and gene dosage alteration of FRMPD2 has been observed, its role in the nervous system remains unknown. Therefore, I investigated the role of FRMPD2 in neurodevelopment. I found that FRMPD2 localizes at the excitatory synapses and promotes synaptogenesis in rat neurons. Mechanistically, FERM domain is required for synaptic localization of FRMPD2 through the interaction with F-actin in spines. More importantly, I found that FRMPD2 associates with cell adhesion molecule Neuroligin-1 through PDZ domain mediated interaction, resulting in an increase in Neuroligin-1 surface expression and up-regulation of synaptogenesis. Results from in utero electroporation showed that overexpression of FRMPD2 in mouse brains delayed neuronal migration and increased dendritic arborization and spine formation. Remarkably, viral overexpression of FRMPD2 in mouse brains improved memory retention. Abnormalities in synaptogenesis during neurodevelopment can cause neurodevelopmental disorders, such as Autism Spectrum Disorders (ASDs). Genomic studies from cohorts of ASD patients have revealed the prevalence of dysfunctional genes in the ubiquitin-proteasome pathway, especially the E3 ligases, suggesting the E3 ligase as a key component in ASD pathogenesis. Genomic duplication or deletion of PARK2 gene, a E3 ligase gene, has been identified in ASD patients. Therefore, I explored the autistic phenotypes of the Park2 knockout (KO) mice. Indeed, the KO mice demonstrated features of typical ASD behaviors. Further, Park2 KO mice showed a reduction in spine number, dendritic arborization, and levels of neuronal activity. The alterations in synaptic property in Park2 KO mice may serve as the etiological factor for ASD. These findings provide insights into the role of a novel synaptic organizer scaffold protein for synapse formation during brain development, and a novel ASD model. / 2020-11-12T00:00:00Z

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects communication, socialization, and restricted/repetitive behaviors. In 2012, one out of every 55 children (1 in 42 boys and 1 in 189 girls) have been diagnosed with ASD in the United States. Only 30-40% of ASD has a known etiology (e.g., genetic predisposition) and the other 60-70% is unknown. Prior to this study, there was no known literature on age and gender differences related to neuro-developmental functioning of ASD. The purpose of this study was to examine how the differences in age and gender of people with ASD were related to total and domain scores, as measured by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). This quantitative research study included a sample size of 80 and 2 independent variables: age groupings (ages 1-4, 5-8, 9-17, and 18-older), and gender (male and female). The 4 dependent variables were the total and domain scores measured by the ADOS-2. The statistical analyses included a multiple analysis of variance (MANOVA) and a 2-way analysis of variance (ANOVA) to examine age and gender differences in the ADOS-2 domain and total scores. There was a statistically signi�cant difference for age on the domain dependent variables, F(9, 171) = 2.64, p = .007; Wilks' Lambda = .73; partial η2 = .10. However, there were no statistically significant differences for gender on domain scores and there were no statistically significant differences for age and gender on the overall scores. Those with ASD between ages 5-8 were more severely impaired for socialization when compared to other age groups and other domains. This research can be used for the improvement of intervention strategies for the diverse ASD population, and to improve the understanding of the neurodevelopmental functioning of individuals with ASD based on age and gender.

No description available.

The purpose of this study was to examine the effects that aerobic exercise activities can have on various stereotypical behaviors found in children on the autism spectrum. Autism spectrum disorder (ASD) is a lifelong, developmental disability that can impact how an individual communicates, behaves, as well as moves. Physical activity has long been implemented in the treatment plans of children with diagnoses along the autism spectrum; However, specific data relating to the impact of aerobic activity is quite scattered. Aerobic activities require the body to be able to take oxygen from the air around it and circulate it through the blood as a form of energy production and can include exercises of low to high intensity. This strain on the cardiovascular system then stimulates behaviors for a child with ASD. By using systematic literature review methodology this study discusses the benefits that aerobic activities, in particular, can have on the many stereotypical behaviors found in children on the autism spectrum including, irregular sleep patterns, shortened attention spans, repetitive movements, as well as overall wellness and the health improvements that arise as a result of this physical activity. Results from this review indicate that there is a positive correlation between increased aerobic activities and a decline in stereotypical behavior in children on the autism spectrum, however, the long-term effects of this practice are not discussed in this literature review.

Syftet med denna studie var att bidra med ökad kunskap om framgångsrika undervisningsstrategier i läsförståelse för elever med autism genom att intervjua 15 pedagoger verksamma i reguljär grundskola och resursskola. Studien utgick från ett sociokulturellt perspektiv på lärande där lärande sker i meningsfulla sammanhang i samspel och kommunikation med andra. Studien har en kvalitativ ansats med semistrukturerade intervjuer av 15 pedagoger som hade erfarenheter av att undervisa elever med ASD, Autism Spectrum Disorder, i åk 1-9 i läsförståelse. Resultatet visade både likheter och skillnader i pedagogernas upplevelser och erfarenheter. En likhet som framträdde i resultatet var att elevernas motivation för det lästa upplevdes som avgörande för läsning och att det användes i undervisningen.  Vidare beskrevs utmaningar för eleverna med ASD att koppla det lästa till egna erfarenheter och att läsa mellan raderna. Pedagogerna använde sig ofta av modellering som undervisningsstrategi för läsförståelse. En likhet som beskrevs var att det sällan var svårigheter med avkodning för elevgruppen utan att läsförståelsen var det område som skapade svårigheter. Resultatet visade att utmaningar med läsförståelse för elever med ASD inte enbart förklarades med teorin The Simple View of Reading där läsförståelse anses vara produkten av avkodning och språkförståelse. Istället beskrevs utmaningar med läsförståelse för elever med ASD som kunde förklaras med exekutiva funktioner och den nedsättning i förmåga som tillskrivs diagnosen ASD.  Skillnader som framträdde var pedagogernas resonemang i de olika verksamheterna vad gällde bedömning och huruvida det var fungerande kartläggningsmaterial även för elever med ASD. I resursskolorna uppmärksammades nationella bedömningsstöd och kartläggningsmaterial som begränsade vad gällde att fånga dessa elevers kompetenser medan materialet i den reguljära skolan upplevdes uppmärksamma svårigheter i läsförståelse på ett likvärdigt sätt som för elever utan ASD. Skillnader var också hur undervisningssituationen organiserades. I den reguljära skolan deltog ofta eleverna med ASD i större elevgrupper med inslag av kooperativt lärande och cirkelmodellen som arbetsmetod. I resursskolan undervisades eleverna med ASD i mindre grupper tillsammans med andra elever med olika NPF och de undervisades med nära stöd av pedagog. I resursskolan hade samtliga tagit del av utbildning genom arbetsplatsen samt sökte i högre grad än i den reguljära skolan litteratur på egen hand. I uppsatsen beskrivs olika specialpedagogiska perspektiv samt inkluderingsbegrepp för att nyansera de olika verksamheterna.

No description available.

Background: Autism spectrum disorder (ASD) is a lifelong developmental disability defined by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. Over the last few decades, the global prevalence of autism has increased by twentyfold to thirtyfold. In the United States, the prevalence of ASD has increased rapidly with one out of every fifty-nine children (1.7%) diagnosed with the condition. With the increasing prevalence of ASD, the financial cost has been estimated to exceed those of Diabetes and Attention Deficit Hyperactivity Disorder (ADHD) by 2025. Furthermore, ASD has been found to be about 4-5 times more prevalent in males, compared to females, and there has been a noted increase in the prevalence of congenital abnormalities in patients with ASD. Objective: As part of an ongoing multi-year retrospective chart review of the patients seen at the Genetics Clinic for suspected or confirmed cases of ASD, we sought to identify the demographic characteristics of these patients and to see how they compare with documented studies. Methods: The overall study is an ongoing multi-year, retrospective chart review of patients seen at the ETSU Medical Genetics Clinic, with features suggestive of ASD. For this preliminary study, we extracted data from the Electronic health record (Allscripts) for 80 patients (n=80), on the gender, term status at birth (term defined as gestational age at delivery of 37 weeks or more, preterm defined as those delivered at less than 37 weeks), twin status, presence of congenital abnormalities, and the state of residence. We entered all the extracted data into REDCap and carried out a descriptive analysis of the data using the Statistical Package for Social Sciences (SPSS). Results: It was found that of the eighty patients, eighteen (22.5%) were females while sixty-two (77.5%) were males, (male to female ratio of 3.4 to 1). Fifty-nine patients (73.8%) were born at term, eighteen (22.5%) born preterm and three (3.8%) with unknown term status. Seventy-seven patients (96.3%) were twins and three (3.8%) were not. Thirty patients (37.5%) had no congenital abnormalities at birth while fifty patients (62.5%) had at least one congenital abnormality at birth. Sixty-one patients (76.3%) were from Tennessee while nineteen (23.8%) were from Virginia. Conclusions: This preliminary finding revealed an increased proportion of males compared to females, as well as an increased proportion of the population with congenital abnormalities compared to those without such abnormality. These findings agree with documented data from previous studies on ASD. In our future analysis, we would examine the rate of diagnosis of ASD in the clinic, the type of mutation and the genes involved and identify any trend for specific genes, and/or specific mutation.

This study examined the use of a humanoid robot to engage two children with Autism Spectrum Disorder (ASD) on responding language behaviors including language, affect, imitation, and eye contact. The robot was integrated into each child's regular intervention in low-doses (10 min of a 50 min session). The goal was to increase responding language behaviors in the children with their conversational partners. The two children participated in pre and post assessment sessions as well as 16 intervention sessions. The data from these sessions were coded into two main categories including how the children interacted (Initiating Engagement, Responding to Engagement, and Non-Engagement) and who the children interacted with (Robot Only and Both). Both children improved in response to the intervention indicating a relation between improved behavior and intervention with the robot.

Autism Spectrum Disorder (ASD) is an intricate and complex disorder that continues to grow in its prevalence year after year. The disorder is based on decreased social communication with prevalent stereotypical behaviors and problems in sensory processing. Due to the disorder diagnosis based on a spectrum, each child is different in their severity, and thus requires individualized forms of therapies and treatments. The cause of ASD is unknown, which makes the treatment difficult to standardize. Desperate to find a regimen that benefits their child’s ability to function more successfully, more and more parents are utilizing complementary alternative medicine (CAM). The problem with CAM is lack of evidence that supports using CAM practice. One example of CAM is hippotherapy, which is a type of intervention used by physical, occupational and speech therapists which uses the movements of a horse to address a patient’s impairments physically, emotionally and neurologically. Hippotherapy has been used since the 1960s for a number of disorders. This systematic literature review examines the effects of hippotherapy for children with ASD in regards to increasing social communication and decreasing stereotypical behaviors. The conclusion of the review resulted in conflicting evidence regarding the efficacy of hippotherapy for children with ASD. This inconclusive lack of evidence is generally due to the lack of standardized measurement scales or treatment plans used during each session and small sample sizes.

Propionic acid (PPA) is a short chain fatty acid that is produced by the human gut microbiome. Propionate, butyrate and acetates are the end products of the fermentation of the complex carbohydrates by human gut friendly microbiome and are being used as sources of energy in our body. PPA is used as a food preservative against molds in various daily products and has been implicated in the pathogenesis of autism. In a recent study we showed that PPA in human neuronal stem cell (NSC) culture increases the astrocyte population and decreases the neuronal number and increases the inflammatory cytokines. In this study, we investigated the potential effects of a propionic acid-derivative, Ibuprofen, a member of the non-steroidal anti-inflammatory drugs (NSAIDs) on neural stem cells proliferation and differentiation in vitro. Ibuprofen is an over counter drug that is used for alleviating pain, headache, and fever. To examine the effect of ibuprofen on developing brain we used human NSC in vitro, exposed them to increasing concentrations of ibuprofen, and investigated neural proliferation and differentiation. Here we show that NSAIDs, not at therapeutic, but very high concentrations cause an imbalance in NSC differentiation towards glial cells, therefore causing astrogliosis seen in some cases of autism spectrum disorder (ASD). Furthermore, upon removal of Ibuprofen, inflammatory cytokines; TNF-alpha, IL-6 and IL-10, significantly increase (p < 0.05) in cells previously exposed to NSAIDs compared to control. Therefore, we are speculating that if such drugs were to be taken in the circumstances of a developing child during the early trimesters of pregnancy, this could result in increased glial:neuron ratio leading to lifelong impediments. Based on the current study our recommendation is to avoid high doses of propionic acid derivatives such as ibuprofen during pregnancy.