• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.389-396
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• 2020

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.

• Clinical and Experimental Pediatrics
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• v.58 no.1
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• pp.8-14
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• 2015

In patients with a language developmental delay, it is necessary to make a differential diagnosis for autism spectrum disorders (ASDs), specific language impairment, and mental retardation. It is important that pediatricians recognize the signs and symptoms of ASDs, as many patients with language developmental delays are ultimately diagnosed with ASDs. Pediatricians play an important role in the early recognition of ASDs, because they are usually the first point of contact for children with ASDs. A revision of the diagnostic criteria of ASDs was proposed in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) that was released in May 2013. The autism spectrum describes a range of conditions classified as neurodevelopmental disorders in the fifth edition of the DSM. The new diagnostic criteria encompasses previous elements from the diagnosis of autistic disorder, Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder-not otherwise specified. An additional change to the DSM includes synthesizing the section on social and communication deficits into one domain. In ASD patients, the appropriate behavioral therapies and rehabilitation treatments significantly affect the prognosis. Therefore, this makes early diagnosis and treatment very important. In conclusion, pediatricians need to be able to recognize the signs and symptoms of ASDs and be attentive to them in order to make an early diagnosis and provide treatment.

• Molecules and Cells
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• v.41 no.10
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• pp.881-888
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• 2018

During the cortical development, cells in the brain acquire somatic mutations that can be implicated in various neurodevelopmental disorders. There is increasing evidence that brain somatic mutations lead to sporadic form of epileptic disorders with previously unknown etiology. In particular, malformation of cortical developments (MCD), ganglioglioma (GG) associated with intractable epilepsy and non-lesional focal epilepsy (NLFE) are known to be attributable to brain somatic mutations in mTOR pathway genes and others. In order to identify such somatic mutations presenting as low-level in epileptic brain tissues, the mutated cells should be enriched and sequenced with high-depth coverage. Nevertheless, there are a lot of technical limitations to accurately detect low-level of somatic mutations. Also, it is important to validate whether identified somatic mutations are truly causative for epileptic seizures or not. Furthermore, it will be necessary to understand the molecular mechanism of how brain somatic mutations disturb neuronal circuitry since epilepsy is a typical example of neural network disorder. In this review, we overview current genetic techniques and experimental tools in neuroscience that can address the existence and significance of brain somatic mutations in epileptic disorders as well as their effect on neuronal circuitry.

• Molecules and Cells
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• v.42 no.12
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• pp.828-835
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• 2019

PIWI Argonaute proteins and Piwi-interacting RNAs (piRNAs) are expressed in all animal species and play a critical role in cellular defense by inhibiting the activation of transposable elements in the germline. Recently, new evidence suggests that PIWI proteins and piRNAs also play important roles in various somatic tissues, including neurons. This review summarizes the neuronal functions of the PIWI-piRNA pathway in multiple animal species, including their involvement in axon regeneration, behavior, memory formation, and transgenerational epigenetic inheritance of adaptive memory. This review also discusses the consequences of dysregulation of neuronal PIWI-piRNA pathways in certain neurological disorders, including neurodevelopmental and neurodegenerative diseases. A full understanding of neuronal PIWI-piRNA pathways will ultimately provide novel insights into small RNA biology and could potentially provide precise targets for therapeutic applications.

• Korean Journal of Occupational Therapy
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• v.26 no.4
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• pp.27-41
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• 2018

Objective : This study implemented occupation-based practice as a group program for children with neurodevelopmental disabilities, and investigated the quality of occupational performance, performance and satisfaction, and efficacy levels of the program. Methods : ADOC-S(Aid for Decision making in Occupation Choice-School) and COPM(Canadian Occupational Performance Measure) were used to establish common meaningful occupational goals for 10 children with neurodevelopmental disabilities. After occupational analysis of the 'subway use', the Performance Quality Rating Scale(PQRS) were used to evaluate the quality of occupational performance. Occupation-based interventions were implemented by participants individually performing meaningful occupations in the most natural and real-life environments as possible. The trial consisted of 1 session of pre-intervention assessments, 8 sessions of intervention, where a single session of 100 minutes is provided once a week. Post-intervention evaluation was conducted over one session. Results : The quality of occupational performance by PQRS was 38.10 higher than before intervention. The occupation-based intervention as a group program used the maintain and modify(compensation, adaptation) approaches and acquisition model. In the early stages of intervention (1 to 4 sessions), the occupational performance was greatly improved. The performance level of COPM increased by 5.80 and the satisfaction level was increased by 7.00. In addition, high scores were found in program satisfaction through parental interview. Conclusion : The results of implementing occupation-based interventions to children with neurodevelopmental disabilities showed increase in quality of occupational performance, performance, and satisfaction along with positive effects of satisfaction levels for the program.

• Journal of Life Science
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• v.33 no.4
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• pp.371-381
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• 2023

Endocrine disrupting chemicals (EDCs), used in a variety of products in modern society, are hormone-like substances that cause various diseases. Humans are exposed to EDCs through their inclusion in pesticides, plastics, cosmetics, detergents, and drugs. Bisphenol A (BPA), one of the representative endocrine disruptors, is an estrogen-like substance that has been widely used commercially in plastic and epoxy resins. BPA is a chemical that can disrupt the endocrine system, leading to reduced reproductive function, obesity, cancer, and neurodevelopmental disorders. Since the adverse health effects of BPA began to be reported the use of BPA has been regulated worldwide. Various alternatives to BPA have been widely used worldwide; representatively, bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used in commercial contexts. BPS and BPF may cause endocrine-disrupting effects like those of BPA due to their similar chemical structures. Recent studies have reported that BPS and BPF disrupt the neurodevelopmental process and cause neurodevelopmental disorders. Therefore, future studies will be required for safety verification of BPA alternatives and the development of new alternatives to BPA for brain health. In this review, we reviewed the effects of BPA and the alternatives, BPS and BPF, on the nervous system.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.2
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• pp.183-191
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• 2005

Tic disorder including Tourette's disorder is a neurodevelopmental disorder that appears in childhood and characterized by the presence of motor and vocal tics. Childhood-onset obsessive-compulsive disorder (OCD) is suggested to be a phenomenologically and etiologically distinct subtype of OCD, bearing a close genetic relationship to tic-disorders. Tourette's disorder and OCD are comorbid in $40-75\%$ of patients initially diagnosed with either disorder. Basal ganglia and cortico-striato-thalamic circuits are implicated in the pathophysiology of both disorders and these disorders have similar clinical features. Over the past decades, the progress in research on Tourette's disorder and OCD has been extraordinary. This review describes some of important insights from these work, involving these areas : 1) clinical implication 2) genetics and epidemiology 3) brain imaging study 4) neuroche-mistry 5) pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS).

• Journal of Life Science
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• v.32 no.1
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• pp.70-77
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• 2022

Endocrine disrupting chemicals (EDCs) have been attracting significant attention in modern society, owing to the increased incidence rate of various diseases along with population growth. EDCs are found in many commercial products, including some plastic bottles and containers, detergents, liners of metal food cans, flame retardants, food, toys, cosmetics, and pesticides. EDCs have a hormonal effect on the human body, which disrupts the endocrine system, notably affecting sexual differentiation and normal reproduction, and can trigger cancer as well. Recently, the association between neurological diseases and EDCs has become a hot topic of research in the field of neuroscience. Considering that EDCs negatively affect not only neuronal proliferation and neurotransmission but also the formation of the neuronal networks, EDCs may induce neurodevelopmental disorders, such as autism spectrum disorders and attention-deficit/hyperactivity disorder as well as neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. In light of these potentially deleterious outcomes, important efforts have been underway to minimize the exposure to EDCs through appropriate regulations and policies around the world, but chemicals that have not yet been associated with endocrine disrupting properties are still in wide use. Therefore, more epidemiological investigations and research are needed to fully understand the effects of EDCs on the nervous system.

• Clinical and Experimental Pediatrics
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• v.63 no.9
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• pp.368-372
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• 2020

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by impairments in social interaction and verbal and nonverbal communication. Purpose: Determine the association between use of assisted reproduction technology (ART) and the risk of ASD among children. Methods: This case-control study included 300 participants (100 cases, 200 controls). The control group included women with a child aged 2-10 years without ASD, while the cases were women with a child aged 2-10 years with ASD. We used a researcher-made questionnaire. Data were analyzed using Stata ver. 14 at the 0.05 significance level. Results: In the univariate analysis, there was significant association between child sex, delivery mode, history of preterm delivery, history of using ART, and maternal age at child's birth and the risk of ASD. After the adjustment for other variables, this association was significant for male sex (2.66; 95% confidence interval [CI], 1.11-4.31; P=0.001) and history of using ART (4.03; 95% CI, 1.76-9.21; P=0.001). Therefore, after the adjustment for confounder variables, there was no significant association between ART and the risk of ASD among children (4.98; 95% CI, 0.91-27.30; P=0.065). Conclusion: After the adjustment for other variables, risk factors for ASD were male sex and history preterm delivery. Thus, there was no significant association between ART and the risk of ASD among children.

• Journal of Genetic Medicine
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• v.13 no.1
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• pp.1-13
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• 2016

Although some mutations are beneficial and are the driving force behind evolution, it is important to maintain DNA integrity and stability because it contains genetic information. However, in the oxygen-rich environment we live in, the DNA molecule is under constant threat from endogenous or exogenous insults. DNA damage could trigger the DNA damage response (DDR), which involves DNA repair, the regulation of cell cycle checkpoints, and the induction of programmed cell death or senescence. Dysregulation of these physiological responses to DNA damage causes developmental defects, neurological defects, premature aging, infertility, immune system defects, and tumors in humans. Some human syndromes are characterized by unique neurological phenotypes including microcephaly, mental retardation, ataxia, neurodegeneration, and neuropathy, suggesting a direct link between genomic instability resulting from defective DDR and neuropathology. In this review, rare human genetic disorders related to abnormal DDR and damage repair with neural defects will be discussed.