The epigenetic regulation of synaptic genes contributes to the etiology of autism

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Annamaria Srancikova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Epigenetic Regulation ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Prader Willi Syndrome ◽  
Epigenetic Mechanisms ◽  
Substantial Evidence ◽  
Autistic Symptoms ◽  
Spectrum Disorders ◽  
The Brain

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.

scholarly journals The Role of Iron in the Pathogenesis of Autism Spectrum Disorders in Children

2018 ◽  
Vol 17 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Olga V. Kostina
Keyword(s):  
Autism Spectrum Disorders ◽  
Iron Metabolism ◽  
Biochemical Parameters ◽  
Children With Autism ◽  
Neuropsychiatric Disorders ◽  
Perinatal Period ◽  
Autism Spectrum ◽  
Spectrum Disorders ◽  
The Brain

The review presents an analysis of the mechanisms of iron effect on the brain development. The importance of iron deficiency in the perinatal period is considered as a risk factor for the development of neuropsychiatric disorders in children with autism spectrum disorders (ASDs). Possible causes of sideropenia are discussed; data on haematological and biochemical parameters characterizing iron metabolism in children with ASDs are presented. The demand for studying the role of iron metabolism imbalance in the development of neuropsychiatric disorders in order to clarify pathogenetic mechanisms of ASDs and to determine methods for their correction is emphasized.

scholarly journals Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms

2014 ◽  
Vol 5 ◽  
Author(s):  
Sylvie Tordjman ◽  
Eszter Somogyi ◽  
Nathalie Coulon ◽  
Solenn Kermarrec ◽  
David Cohen ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Autism Spectrum ◽  
Epigenetic Mechanisms ◽  
Spectrum Disorders

scholarly journals Potential Novel Therapies for Neurodevelopmental Diseases Targeting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Alexandrina S. Curpan ◽  
Alina-Costina Luca ◽  
Alin Ciobica
Keyword(s):  
Oxidative Stress ◽  
Neurodevelopmental Disorders ◽  
Antioxidant Properties ◽  
Autism Spectrum ◽  
Oxidative Status ◽  
Glutathione Level ◽  
Aspartate Receptor ◽  
Spectrum Disorders ◽  
The Impact ◽  
The Brain

Neurodevelopmental disorders are a category of diseases that is not yet fully understood. Due to their common traits and pathways, often it is difficult to differentiate between them based on their symptoms only. A series of hypotheses are trying to define their etiology, such as neuroinflammation, neurodegeneration, and immunology, but none have managed to explain their multifactorial manifestation. One feature that may link all theories is that of oxidative stress, with a redox imbalance as well as several other markers of oxidative damage (on lipids, proteins, and nucleic acids) being observed in both postmortem samples of the brain of patients with schizophrenia and autism spectrum disorders. However, the implication of oxidative stress in pathology is still distrustfully looked upon. For this purpose, in the current paper, we were interested in reviewing the implications of oxidative stress in these disorders as well as the impact of N-acetylcysteine on the oxidative status with a focus on the glutathione level and N-methyl-D-aspartate receptor. We were also interested in finding papers targeting the use of antioxidant properties of different plant extracts.

scholarly journals Essential role of the nuclear isoform of RBFOX1, a candidate gene for autism spectrum disorders, in the brain development

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nanako Hamada ◽  
Hidenori Ito ◽  
Takuma Nishijo ◽  
Ikuko Iwamoto ◽  
Rika Morishita ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Brain Development ◽  
Candidate Gene ◽  
Essential Role ◽  
Autism Spectrum ◽  
Spectrum Disorders ◽  
The Brain

scholarly journals A healthy gut for a healthy brain: preclinical, clinical and regulatory aspects

2020 ◽  
Vol 18 ◽  
Author(s):  
Carla Petrella ◽  
Stefano Farioli-Vecchioli ◽  
Giusy Ylenia Cisale ◽  
Georgios Strimpakos ◽  
John Joseph Borg ◽  
...  
Keyword(s):  
Neurodevelopmental Disorder ◽  
Large Body ◽  
Food Supplement ◽  
Autism Spectrum ◽  
Pathological Conditions ◽  
Spectrum Disorders ◽  
Dietary Strategies ◽  
The Brain ◽  
Brain Homeostasis

: A large body of research has shown the presence of a complex pathway of communications between the gut and the brain. It is now recognized that, through this pathway, the microbiota can influence brain homeostasis and plasticity under normal and pathological conditions. This review aims at providing an overview of preclinical and clinical pieces of evidence supporting the possible role of gutbrain axis modulation in physiological aging, in a neurodevelopmental disorder, the autism spectrum disorders and in a substance abuse disorder, the alcohol addiction. Since the normalization of gut flora can prevent changes in the behavior, we postulate that the gut-brain axis might represent a possible target for pharmacological and dietary strategies aimed at improving not only intestinal but also mental health. The present review also reports some regulatory considerations regarding the use of probiotics, illustrating the most debated issues about the possibility of considering probiotics not only as a food supplement but also as a “full” medicinal product.

scholarly journals The Impact of Gut Microbiota-Derived Metabolites in Autism Spectrum Disorders

2021 ◽  
Vol 22 (18) ◽  
pp. 10052
Author(s):  
Lucía N. Peralta-Marzal ◽  
Naika Prince ◽  
Djordje Bajic ◽  
Léa Roussin ◽  
Laurent Naudon ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neurodevelopmental Disorders ◽  
Specific Treatment ◽  
Autism Spectrum ◽  
Microbial Composition ◽  
Host Interactions ◽  
Bidirectional Communication ◽  
Spectrum Disorders ◽  
The Impact ◽  
The Brain

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome–host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.

scholarly journals Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuki Murakami ◽  
Yukio Imamura ◽  
Kuniaki Saito ◽  
Daisuke Sakai ◽  
Jun Motoyama
Keyword(s):  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Kynurenine Pathway ◽  
Autism Spectrum ◽  
Behavioral Deficits ◽  
Diagnostic Biomarkers ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders ◽  
Almost All ◽  
The Brain

Abstract Deleterious mutations in patchd1 domain containing 1 (PTCHD1) gene have been identified in patients with intellectual disability and/or autism spectrum disorder (ASD). To clarify the causal relationship between Ptchd1 deficiency and behavioral defects relevant to neurodevelopmental disorders, we generated global Ptchd1 knockout (KO) mice. Ptchd1 KO mice displayed hyperlocomotion, increased impulsivity, and lower recognition memory, which resemble attention-deficit hyperactivity disorder (ADHD)-like behaviors. Acute or chronic treatment with atomoxetine ameliorated almost all behavioral deficits in Pthcd1 KO mice. We next determined possible involvement of the kynurenine pathway (KP) metabolites in neurodevelopmental disorders in Ptchd1 KO mice and assessed the potential of KP metabolites as biomarkers for ADHD and/or ASD. Ptchd1 KO mice showed drastic changes in KP metabolite concentrations in the serum and the brain, indicating that the activated KP is associated with ADHD-like behaviors. Our findings indicate that Ptchd1 KO mice can be used as an animal model of human ADHD and/or ASD, and KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.

scholarly journals The Multifaceted Roles of Primary Cilia in the Development of the Cerebral Cortex

2021 ◽  
Vol 9 ◽  
Author(s):  
Kerstin Hasenpusch-Theil ◽  
Thomas Theil
Keyword(s):  
Cerebral Cortex ◽  
Neurodevelopmental Disorders ◽  
Primary Cilia ◽  
Autism Spectrum ◽  
Multiple Roles ◽  
Axon Pathfinding ◽  
Spectrum Disorders ◽  
Circuit Formation ◽  
Multiple Signaling ◽  
The Brain

The primary cilium, a microtubule based organelle protruding from the cell surface and acting as an antenna in multiple signaling pathways, takes center stage in the formation of the cerebral cortex, the part of the brain that performs highly complex neural tasks and confers humans with their unique cognitive capabilities. These activities require dozens of different types of neurons that are interconnected in complex ways. Due to this complexity, corticogenesis has been regarded as one of the most complex developmental processes and cortical malformations underlie a number of neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, and epilepsy. Cortical development involves several steps controlled by cell–cell signaling. In fact, recent findings have implicated cilia in diverse processes such as neurogenesis, neuronal migration, axon pathfinding, and circuit formation in the developing cortex. Here, we will review recent advances on the multiple roles of cilia during cortex formation and will discuss the implications for a better understanding of the disease mechanisms underlying neurodevelopmental disorders.

scholarly journals Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders

2021 ◽  
Author(s):  
Sébastien Delhaye ◽  
Barbara Bardoni
Keyword(s):  
Autism Spectrum Disorders ◽  
Intellectual Disability ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Significant Advance ◽  
Main Function ◽  
Pde Inhibitors ◽  
Spectrum Disorders ◽  
Camp And Cgmp

AbstractPhosphodiesterases (PDEs) are enzymes involved in the homeostasis of both cAMP and cGMP. They are members of a family of proteins that includes 11 subfamilies with different substrate specificities. Their main function is to catalyze the hydrolysis of cAMP, cGMP, or both. cAMP and cGMP are two key second messengers that modulate a wide array of intracellular processes and neurobehavioral functions, including memory and cognition. Even if these enzymes are present in all tissues, we focused on those PDEs that are expressed in the brain. We took into consideration genetic variants in patients affected by neurodevelopmental disorders, phenotypes of animal models, and pharmacological effects of PDE inhibitors, a class of drugs in rapid evolution and increasing application to brain disorders. Collectively, these data indicate the potential of PDE modulators to treat neurodevelopmental diseases characterized by learning and memory impairment, alteration of behaviors associated with depression, and deficits in social interaction. Indeed, clinical trials are in progress to treat patients with Alzheimer’s disease, schizophrenia, depression, and autism spectrum disorders. Among the most recent results, the application of some PDE inhibitors (PDE2A, PDE3, PDE4/4D, and PDE10A) to treat neurodevelopmental diseases, including autism spectrum disorders and intellectual disability, is a significant advance, since no specific therapies are available for these disorders that have a large prevalence. In addition, to highlight the role of several PDEs in normal and pathological neurodevelopment, we focused here on the deregulation of cAMP and/or cGMP in Down Syndrome, Fragile X Syndrome, Rett Syndrome, and intellectual disability associated with the CC2D1A gene.

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