• International Journal of Stem Cells
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• v.15 no.1
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• pp.26-40
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• 2022

Region specific brain organoids are brain organoids derived by patterning protocols using extrinsic signals as opposed to cerebral organoids obtained by self-patterning. The main focus of this review is to discuss various region-specific brain organoids developed so far and their application in modeling neurodevelopmental disease. We first discuss the principles of neural axis formation by series of growth factors, such as SHH, WNT, BMP signalings, that are critical to generate various region-specific brain organoids. Then we discuss various neurodevelopmental disorders modeled so far with these region-specific brain organoids, and findings made on mechanism and treatment options for neurodevelopmental disorders (NDD).

• Environmental Analysis Health and Toxicology
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• v.25 no.4
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• pp.259-262
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• 2010

In this review, we give an overview of psychiatric perspectives on environmental disease. The concept of genetic heritability and its meaning with regard to environmental risk factors will be discussed. Recent ideas of gene-environment interaction and neurodevelopmental disorder in psychiatry will also be introduced. This article discusses the environmental risk factors for attention deficit hyperactivity disorder (ADHD) and autism, the two major environmental diseases and neurodevelopmental disorders in psychiatry. Given that both ADHD and autism are complex conditions, the etiology is likely to involve multiple genes of moderate effect interacting with environmental factors. We will introduce recent environmental issues related to these two disorders.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.94-99
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• 2022

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited purine metabolic disorder that accompanies neurodevelopmental problems. Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant inherited genetic disorder characterized by tumors in various systems. Some children with NF1 also accompanies neurodevelopmental problems. Here, we describe a 5-year-old boy with a maternally inherited pathogenic variant in NF1 and hypoxanthine-guanine phosphoribosyltransferase (HPRT). He was referred for severe neurodevelopmental impairment and hyperuricemia. His mother was diagnosed with NF1 and the patient was also suspected of having NF1 because of cafe au lait macules. He had dystonia, rigidity, cognitive deficit, and speech/language impairment. Serum and urine uric acid concentrations were elevated. He had more severe neurodevelopmental delay than patients with only NF1, so his clinical symptoms could not be fully understood by the disease alone. To find the cause of his neurologic symptoms and hyperuricemia, the patient and his mother underwent a whole-exome sequencing test. As a result, the pathogenic variant c.151C>T (p.Arg51Ter) in HPRT1 was identified as hemizygote in the patient and heterozygote in his mother. The pathogenic variant c.7682C>G (p.Ser2561Ter) in NF-1 was identified as heterozygotes in both of them. Although the clinical symptoms of both diseases were overlapping and complicated, genetic testing was helpful for accurate diagnosis and treatment. Therefore, we suggest to consider preemptive genetic evaluation if there are symptoms not sufficiently explained by known existing diseases. And it is considered valuable to review this rare case to understand the clinical course and possible synergic effects of these diseases.

• International Journal of Stem Cells
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• v.15 no.3
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• pp.270-282
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• 2022

Background and Objectives: Menkes disease (MNK) is a rare X-linked recessive disease, caused by mutations in the copper transporting ATP7A gene that is required for copper homeostasis. MNK patients experience various clinical symptoms including neurological defects that are closely related to the prognosis of MNK patients. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) produce new neurons throughout life, and defects in DG neurogenesis are often correlated with cognitive and behavioral problems. However, neurodevelopmental defects in the DG during postnatal period in MNK have not been understood yet. Methods and Results: Mottled-brindled (Mo^Br/y) mice (MNK mice) and littermate controls were used in this study. In vivo microCT imaging and immunohistochemistry results demonstrate that blood vasculatures in hippocampus are abnormally decreased in MNK mice. Furthermore, postnatal establishment of NSC population and their neurogenesis are severely compromised in the DG of MNK mice. In addition, in vitro analyses using hippocampal neurosphere culture followed by immunocytochemistry and immunoblotting suggest that neurogenesis from MNK NSCs is also significantly compromised, corresponding to defective neurogenic gene expression in MNK derived neurons. Conclusions: Our study is the first reports demonstrating that improper expansion of the postnatal NSC population followed by significant reduction of neurogenesis may contribute to neurodevelopmental symptoms in MNK. In conclusion, our results provide new insight into early neurodevelopmental defects in MNK and emphasize the needs for early diagnosis and new therapeutic strategies in the postnatal central nerve system damage of MNK patients.

• Clinical and Experimental Pediatrics
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• v.57 no.3
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• pp.101-109
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• 2014

The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.

• Journal of Ginseng Research
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• v.37 no.1
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• pp.8-29
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• 2013

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

• BMB Reports
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• v.53 no.10
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• pp.500-511
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• 2020

14-3-3 proteins are mostly expressed in the brain and are closely involved in numerous brain functions and various brain disorders. Among the isotypes of the 14-3-3 proteins, 14-3-3γ is mainly expressed in neurons and is highly produced during brain development, which could indicate that it has a significance in neural development. Furthermore, the distinctive levels of temporally and locally regulated 14-3-3γ expression in various brain disorders suggest that it could play a substantial role in brain plasticity of the diseased states. In this review, we introduce the various brain disorders reported to be involved with 14-3-3γ, and summarize the changes of 14-3-3γ expression in each brain disease. We also discuss the potential of 14-3-3γ for treatment and the importance of research on specific 14-3-3 isotypes for an effective therapeutic approach.

• Neonatal Medicine
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• v.15 no.2
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• pp.123-133
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• 2008

Purpose: The purpose of this study was to determine the outcomes of extremely low birth weight infants (ELBWI) who were born at the Asan Medical Center and evaluate the recent status of neonatal intensive care and associated problems. Methods:We retrospectively evaluated 120 inborn ELBWI who were admitted to the NICU of the Asan Medical Center between 2003 and 2006. The survival rate, neurodevelopmental outcomes, maternal and infant factors, and infant mordibities were evaluated and the relationships with survival and catch-up growth were investigated. Results:The survival rate of the ELBWI was 82% at a mean gestational age of 27+2 weeks, and with a mean birth weight of 801.3${\pm}$129.0 g. The duration of hospitalization was 85.7${\pm}$27.2 days, the duration of O2 use was 43.9${\pm}$35.4 days, and the duration of ventilatory support was 20.9${\pm}$20.9 days among the survivors. The incidence of respiratory distress syndrome, chronic lung disease, severe intraventricular hemorrhage, and periventricular leukomalacia were 41.8%, 61.2%, 3%, and 4%, respectively. The mean mental developmental index and psychomotor development index of Bailey Scales of Infant Development (II) at follow-up were 83.4${\pm}$18.2 and 83.3${\pm}$20.3, respectively. Among the infants who had >18 months of follow-up, 50.8% had catch-up growth at 12 months. Conclusion:The survival rate of ELBWI has improved; however, the morbidities remain high, thus indicating further efforts must be implemented to reduce morbidity and improve neurodevelopmental outcomes.

• Korean Journal of Biological Psychiatry
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• v.20 no.4
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• pp.136-143
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• 2013

Objectives We reviewed cellular and synaptic dysconnectivity, disturbances in micro- and macro- circuitries, and neurodevelopmentally-derived disruptions of neural connectivity in the pathogenesis of schizophrenia. Method We reviewed the selected articles about disturbances in neural circuits which had been proposed as a pathogenetic mechanism of schizophrenia. Results The literature review reveals that schizophrenia may be a disease related to disturbance in neurodevelopmental mechanism, shown as 'a misconnection syndrome of neural circuit or neural network'. In descriptive psychopathological view, definition of a disorder of brain connectivity has limitation to explain other aspects of schizophrenia including deterministic strictness in thought process. Conclusion Schizophrenia is considered as a disorder of brain connectivity as well as a neurodevelopmental disorder related with genetic and environmental factors. We could make a suggestion that "JoHyeonByung (attunement disorder)" denotes the disturbances of psychic fine-tuning which correspond to the neural correlates of brain dysconnectivity metaphorically.

• Journal of Genetic Medicine
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• v.17 no.1
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• pp.43-46
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• 2020

The Shprintzen-Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI. SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.