scholarly journals A Need for Consistency in Behavioral Phenotyping for ASD: Analysis of the Valproic Acid Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Olivia Larner ◽  
Jane Roberts ◽  
Jeffery Twiss ◽  
Linnea Freeman
Keyword(s):  
Valproic Acid ◽  
Neurodevelopmental Disorder ◽  
Signs And Symptoms ◽  
Autism Spectrum ◽  
Rodent Models ◽  
Behavioral Tests ◽  
The Us ◽  
Behavioral Method ◽  
Underlying Mechanisms ◽  
Diagnostic Measurement

Autism spectrum disorder (ASD) is a highly prevalent and impairing neurodevelopmental disorder that affects 1 : 54 persons. Over the last several decades, the reported incidence of ASD in the US has increased potentially due to increased awareness and improved diagnostic measurement. Although ASD prevalence is increasing, the etiology of ASD remains relatively unknown. To better understand the neurological basis of ASD, rodent models of ASD have been developed for research. Currently, there is not a standardized set of behavioral tests to quantify ASD-like behavior in rodents. The goal of this review is to present an overview of the methodologies used to analyze ASD-like behaviors in rodents, focusing on the valproic acid (VPA) model, and illustrate inconsistencies between different approaches. Despite that the in utero VPA rodent model for ASD is widely used and extensively characterized, behaviors vary substantially between different researchers. Moving forward, consistency in behavioral method analytics would benefit progress in evaluating interventions for all models of ASD and help to uncover unique qualities underlying mechanisms causing ASD signs and symptoms.

scholarly journals Central Auditory and Vestibular Dysfunction Are Key Features of Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Yusra Mansour ◽  
Alyson Burchell ◽  
Randy J. Kulesza
Keyword(s):  
Autism Spectrum Disorder ◽  
Auditory Evoked Potentials ◽  
Motor Coordination ◽  
Neurodevelopmental Disorder ◽  
Vestibular Function ◽  
Signs And Symptoms ◽  
Autism Spectrum ◽  
Vestibular Dysfunction ◽  
Repetitive Behaviors ◽  
Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by repetitive behaviors, poor social skills, and difficulties with communication. Beyond these core signs and symptoms, the majority of subjects with ASD have some degree of auditory and vestibular dysfunction. Dysfunction in these sensory modalities is significant as normal cognitive development depends on an accurate representation of our environment. The hearing difficulties in ASD range from deafness to hypersensitivity and subjects with ASD have abnormal sound-evoked brainstem reflexes and brainstem auditory evoked potentials. Vestibular dysfunction in ASD includes postural instability, gait dysfunction, and impaired gaze. Untreated vestibular dysfunction in children can lead to delayed milestones such as sitting and walking and poor motor coordination later in life. Histopathological studies have revealed that subjects with ASD have significantly fewer neurons in the auditory hindbrain and surviving neurons are smaller and dysmorphic. These findings are consistent with auditory dysfunction. Further, the cerebellum was one of the first brain structures implicated in ASD and studies have revealed loss of Purkinje cells and the presence of ectopic neurons. Together, these studies suggest that normal auditory and vestibular function play major roles in the development of language and social abilities, and dysfunction in these systems may contribute to the core symptoms of ASD. Further, auditory and vestibular dysfunction in children may be overlooked or attributed to other neurodevelopmental disorders. Herein we review the literature on auditory and vestibular dysfunction in ASD. Based on these results we developed a brainstem model of central auditory and vestibular dysfunction in ASD and propose that simple, non-invasive but quantitative testing of hearing and vestibular function be added to newborn screening protocols.

scholarly journals A IMPORTÂNCIA DO PROFISSIONAL ENFERMEIRO NO DIAGNÓSTICO DO AUTISMO: uma revisão integrativa da literatura

2020 ◽  
Vol 6 (2) ◽  
pp. 235-245
Author(s):  
Marcelo Cerilo dos Santos-Filho ◽  
◽  
Lais Edvirgens Lima da Cruz ◽  
Bruna Stefany Rocha do Nascimento ◽  
Julyana Constância Feitoza Marinho ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Signs And Symptoms ◽  
Research Problem ◽  
Autism Spectrum ◽  
Diagnostic Process ◽  
Sample Number ◽  
And Behavior ◽  
First Contact ◽  
Nursing Professional

Autism is a neurodevelopmental disorder that damages social interactions, in terms of communication and behavior. As the professional who has the first contact with the child, the nurse must evaluate child development, highlighting the signs that Autism Spectrum Disorder (ASD) presents. Based on what was presented, the current study had as objecitve to present the relevance of the role of nurse in the diagnosis of autism. This research is an integrative and descriptive literature review, and with a qualitative approach of articles published between 2012 and 2019. A search was carried out in the Lilacs, Scielo, Capes Journals and Google Scholar databases. Data collection was carried out between April and October 2019. 908 articles were found, however only 8 responded to the research problem and became the sample number. It was identified that the attention of the nursing professional can not be directed only to the person with autism, but also to their family; it must try to reduce fear, prejudice and the feeling of inferiority towards society. It is the role of nurse to guide family members to communicate with the child, to stimulate their interaction with people. With this, the nurse is essential in the diagnostic process of autism, being aware of the signs and symptoms of autism, providing good nursing care to the child and their relatives, encouraging, transmitting security and tranquility to everyone.

Chronic Testosterone Administration During Pregnancy Causes Autistic-like Traits in Rat Offspring: Possible Relationships with Cerebral Oxytocin, Dopamine, Serotonin and IGF-1 Levels.

2021 ◽  
Author(s):  
Evrim Senkal ◽  
Umut Eryigit ◽  
Mehmet Fatih Bozkurt ◽  
Volkan Solmaz ◽  
Oytun Erbas
Keyword(s):  
Neurodevelopmental Disorder ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Autism Spectrum ◽  
Female Rats ◽  
Behavioral Tests ◽  
Testosterone Undecanoate ◽  
Prenatal Testosterone ◽  
Group 2 ◽  
Group 1

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects boys three times more frequently than girls. Previous studies have suggested that higher fetal testosterone exposure can cause autism-like behaviors in males. The mechanism of effect of fetal testosterone on autism development is not well known. In the present study, we investigated the relationship between prenatal testosterone exposure and ASD in an experimental study with the use of behavioral tests, histopathological examinations and biochemical measurements performed to compare offspring with and without exposure to testosterone. Female rats were randomly distributed into Group 1 (control, n = 6) and Group 2 (Testosterone undecanoate, n = 6). Female rats were caged with a fertile male (three female/one male) for 2–3 days during the oestrus period. Group 1 rats were given 1 ml/kg % 0.9 NaCl saline on the 10th day of pregnancy, while Group 2 rats were given 250 mg/kg testosterone undecanoate. The dams were allowed to raise their litters until weaning on postnatal day 21 (P21). On P21 , forty littermates (10 male control, ten female control, ten male Testosterone-exposed, and ten female Testosterone-exposed) were randomly separated and housed. These animals underwent behavioral testing in adulthood on P50. Subsequently, the rats were sacrificed. Biochemical analyses [Brain tissue 5-Hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), Insulin-like growth factor-1 (IGF-1), and oxytocin] and histopathological analyses were performed. Analysis of the behavioral tests (three-chamber social test, open field test) revealed significant differences among the groups, with the testosterone-exposed groups demonstrating autistic traits at a greater degree. Histologically, hippocampal CA1 and CA3 regions displayed significant alterations such as gliosis and neuronal cell death in the testosterone-exposed groups compared to controls. Brain levels of tissue 5-HIAA, HVA, IGF-1 increased while oxytocin level decreased in the testosterone-exposed groups. These results suggest a possible link between chronic prenatal testosterone exposure and neurodevelopmental disorders such as ASD. Testosterone exposure and autism-like traits can be linked to dopamine, serotonin, IGF-1 increase, and oxytocin decrease.

scholarly journals Introduction

2003 ◽  
Vol 358 (1430) ◽  
pp. 277-280 ◽  
Author(s):  
Uta Frith ◽  
Elisabeth L. Hill
Keyword(s):  
Brain Research ◽  
Neurodevelopmental Disorder ◽  
Signs And Symptoms ◽  
Autism Spectrum ◽  
Processing Style ◽  
Brain Abnormality ◽  
Fast Pace ◽  
Definition Of ◽  
High Level ◽  
Autistic Disorders

Although we know much more now than we did 50 years ago about autism, the nature, origin and even the definition of the condition are still debated and remain largely unknown. This special issue begins with a review of the facts about autistic disorders, as they are known at present. In their introduction, Elizabeth Hill & Uta Frith (2003) remind the reader that autism is no longer regarded as a rare disease. They provide examples of genetic and brain research that targets the biological causes of autism and they review the three major cognitive theories that are currently used to explain the core signs and symptoms of autism. Much more is known now about autism than was known only a few years ago, and there is justified hope that our understanding of autism will continue to accelerate at a fast pace. This issue contains examples of the cutting edge of research and highlights some of the most burning questions. Some of these relate to the diagnosis of Asperger syndrome (AS), the identification of subgroups in the autism spectrum and early signs of autistic disorder. Other questions relate to the brain abnormalities that underlie the putative cognitive deficits and whether these can be made visible through magnetic resonance imaging. The shared assumption among the contributors is that autism is a neurodevelopmental disorder that gives us a unique window on the relationship between mind and brain. The research reported elaborates the key theories that have been put forward to explain the signs and symptoms of autism. These theories try to explain the selective impact of brain abnormality on some of the most high–level mental functions, such as social insight, empathy and information processing style.

Dysregulation of DNA methylation during development as a potential mechanisms contributing to obsessive compulsive disorders and autism

2019 ◽  
Author(s):  
German I. Todorov ◽  
Karthikeyan Mayilvahanan ◽  
David Ashurov ◽  
Catarina Cunha
Keyword(s):  
Mouse Model ◽  
Autism Spectrum ◽  
Obsessive Compulsive ◽  
Cancer Treatments ◽  
Knock Out ◽  
Treatment Priority ◽  
Underlying Mechanisms ◽  
Knock Out Mice ◽  
Obsessive Compulsive Disorders ◽  
Compulsive Disorders

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is raising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behavior and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently lead to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about possible mechanism involved in OCD and ASD. Additionally, it shows that modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of high inherited risk of certain mental health conditions.

Specialized Diet Therapies: Exploration for Improving Behavior in Autism Spectrum Disorder (ASD)

2020 ◽  
Vol 27 (40) ◽  
pp. 6771-6786
Author(s):  
Geir Bjørklund ◽  
Nagwa Abdel Meguid ◽  
Maryam Dadar ◽  
Lyudmila Pivina ◽  
Joanna Kałużna-Czaplińska ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Caloric Intake ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Nutritional Deficiencies ◽  
Childhood And Adolescence ◽  
Restricted Interests ◽  
Balanced Diet ◽  
The Individual

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

scholarly journals FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Reymundo Lozano ◽  
Catherine Gbekie ◽  
Paige M. Siper ◽  
Shubhika Srivastava ◽  
Jeffrey M. Saland ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Medical Assessment ◽  
Forkhead Box ◽  
Organ Systems ◽  
Practice Parameters ◽  
Assessment And Monitoring ◽  
Multidisciplinary Group ◽  
The Brain

AbstractFOXP1 syndrome is a neurodevelopmental disorder caused by mutations or deletions that disrupt the forkhead box protein 1 (FOXP1) gene, which encodes a transcription factor important for the early development of many organ systems, including the brain. Numerous clinical studies have elucidated the role of FOXP1 in neurodevelopment and have characterized a phenotype. FOXP1 syndrome is associated with intellectual disability, language deficits, autism spectrum disorder, hypotonia, and congenital anomalies, including mild dysmorphic features, and brain, cardiac, and urogenital abnormalities. Here, we present a review of human studies summarizing the clinical features of individuals with FOXP1 syndrome and enlist a multidisciplinary group of clinicians (pediatrics, genetics, psychiatry, neurology, cardiology, endocrinology, nephrology, and psychology) to provide recommendations for the assessment of FOXP1 syndrome.

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

scholarly journals Preliminary Results Regarding Sleep in a Zebrafish Model of Autism Spectrum Disorder

2021 ◽  
Vol 11 (5) ◽  
pp. 556
Author(s):  
Madalina Andreea Robea ◽  
Alin Ciobica ◽  
Alexandrina-Stefania Curpan ◽  
Gabriel Plavan ◽  
Stefan Strungaru ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Social Behavior ◽  
Antiepileptic Drug ◽  
Alternative Model ◽  
Neurological Diseases ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Zebrafish Model ◽  
Developmental Defects

Autism spectrum disorder (ASD) is one of the most salient developmental neurological diseases and remarkable similarities have been found between humans and model animals of ASD. A common method of inducing ASD in zebrafish is by administrating valproic acid (VPA), which is an antiepileptic drug that is strongly linked with developmental defects in children. In the present study we replicated and extended the findings of VPA on social behavior in zebrafish by adding several sleep observations. Juvenile zebrafish manifested hyperactivity and an increase in ASD-like social behaviors but, interestingly, only exhibited minimal alterations in sleep. Our study confirmed that VPA can generate specific ASD symptoms, indicating that the zebrafish is an alternative model in this field of research.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

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