• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.399-405
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• 2010

Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex. In a previous study, we reported a developmental increase in $GABA_A$ receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of the induction of long-term synaptic plasticity, in the present study we investigated in detail the postnatal development of phasic and tonic inhibition. The amplitude of phasic inhibition evoked by electrical stimulation increased during development from 3 to 8 weeks of age, and the peak time and decay kinetics of inhibitory postsynaptic potential (IPSP) and current (IPSC) slowed progressively. Since the membrane time constant decreased during this period, passive membrane properties might not be involved in the kinetic changes of IPSP and IPSC. Tonic inhibition, another mode of $GABA_A$ receptor-mediated inhibition, also increased developmentally and reached a plateau at 5 weeks of age. These results indicate that the time course of the postnatal development of GABAergic inhibition matched well that of the functional maturation of the visual cortex. Thus, the present study provides significant insight into the roles of inhibitory development in the functional maturation of the visual cortical circuits.

• International Journal of Oral Biology
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• v.43 no.2
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• pp.93-100
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• 2018

The investigation of the embryonic development of the cerebellum has a long history. The postnatal normal development of the cerebellum in rodents and other animals became a popular topic for morphological investigations nearly a century ago. However, surprisingly, only a few studies are available regarding the prenatal normal development of the rodent cerebellum, especially in guinea pigs. Cell proliferation is essential for the development of the nervous system. The assessment of cell proliferation can be achieved by using various methods. In this study, we investigated the cell proliferation of the cerebellar cortex in guinea pigs at different stages of pregnancy and in postnatal life. Fetuses were obtained by cesarean section at 50 or 60 days of gestation (dg). Immunohistochemistry was performed with proliferating cell nuclear antigen (PCNA) antibody in the cerebellum. Strong PCNA immunoreactivity was observed in the external granular layer (EGL), which is a neurogenic zone in the cerebellum. The proportion of PCNA-IR cells was greater at 1 week than at 60 dg in lobule I, but not lobule VIII. After 50 dg, the width of the EGL continued to decline until 1 week, due to the maturation of the EGL cells. These results demonstrate the pattern of PCNA immunoreactivity in the developing cerebellum of guinea pigs. This serves as a guideline to study abnormal cerebellum development.

• Journal of Animal Science and Technology
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• v.50 no.1
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• pp.45-56
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• 2008

In the present study, real-time PCR was performed to evaluated expression of several isoforms of monocarboxylate transporters(MCTs) and two known MCT regulatory proteins, basigin (Bsg) and embigin, in the epididymis of the male reproductive tract during postnatal development. In addition, ERα�-mediated regulation of MCT1 expression in the epididymis was determined with estrogen receptor(ER) α� knockout(α�ERKO) mice by immunohistochemistry. Results from the current study demonstrated differential expression of MCT isoform(MCT 1, 2, 3, 4, and 8), Bsg, and embigin mRNAs in rat epididymis according to postnatal age and epididymal region. In addition, immunohistochemical study of MCT1 revealed the limited localization of MCT1 at apical area of corpus and caudal epididymis. The present study also showed that expression of MCT1 was not directly regulated by ERα�. The findings from the current study suggest that MCTs would involve in establishing adequate microenvironment for sperm maturation and storage in the epididymis, eventually leading to maintenance of male fertility.

• Development and Reproduction
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• v.19 no.2
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• pp.69-77
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• 2015

Cell-cell direct communication through channel-forming molecules, connexin (Cx), is essential for a tissue to exchange signaling molecules between neighboring cells and establish unique functional characteristics during postnatal development. The corpus epididymis is a well-known androgen-responsive tissue and involves in proper sperm maturation. In the present research, it was attempted to determine if expression of Cx isoforms in the corpus epididymis in the adult is modulated by exposure to estrogenic or anti-androgenic compound during the early postnatal period. The neonatal male rats at 7 days of age were subcutaneously injected by estradiol benzoate (EB) at low-dose ($0.015{\mu}g/kg$ body weight) or high-dose ($1.5{\mu}g/kg$ body weight) or flutamide (Flu) at low-dose ($500{\mu}g/kg$ body weight) or high-dose (50 mg/kg body weight). The corpus epididymis collected at 4 months of age was subjected to evaluate expressional changes of Cx isoforms by quantitative real-time PCR. Treatment of low-dose EB resulted in increases of Cx32, Cx37, and Cx45 transcript levels, while exposure to high-dose EB decreased expression of Cx26, Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45. Treatments of Flu caused significant decreases of expression of all examined Cx isoforms, except Cx37 and Cx43 shown no expressional change with high-dose Flu treatment. These findings imply that expression of most Cx isoforms present in the corpus epididymis would be transcriptionally regulated by actions of androgen and/or estrogen during postnatal period.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.320-327
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• 2022

Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

• Korean Journal of Veterinary Research
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• v.44 no.3
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• pp.335-341
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• 2004

This study was undertaken to examine the developmental expression of osteopontin(OPN) in the mouse brain. In Western blotting analysis, the expression of OPN was noted initially at embryonic stage and increased gradually after birth and decreased at postnatal day 60(P60). In immunohistochemistry, OPN expression was found in the interstitial nucleus Cajal and the substantia nigra reticularis in anterior part of the brain and in the inferior olivary complex, the parabrachial nucleus, the facial nucleus, the gigantocellular reticular nucleus, the trigeminal nucleus and the anterior interposed nucleus in posterior part of the brain at P31 and P60. In addition, OPN expression in widespread neurons appeared during the period of neuronal differentiation, increased just after birth and decreased with maturation. These results suggest that OPN contributes to developmental processes, including the differentiation and maturation of specific neuronal populations.

• Journal of Nutrition and Health
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• v.27 no.9
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• pp.940-948
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• 1994

The present study was designed to determine if prenatal and postnatal Se nutriture affects Se concentration, glutathione peroxidase(GSHPx) activity and phospholipid distribution of the neonatal rat lung. Female SD rats were bred and fed a semipurified Se-deficient(0.04ppm, Se-) or a Se-adequate(0.5ppm, Se+) diet through pregnancy and lactation. On d 2 of lactation, maternal dietary Se had no significant effect on pulmonary Se concentration of pups. On d 16 of lactation, mean milk Se concentration in Se- dams was significantly lower than that in Se+ dams. Milk Se concentration was reflected on lung Se concentration and GSHPx activity of d 16 pups, which were dramatically decreased in Se- pups. In addition, pulmonary disaturated phosphatidyl choline/total phosphatidyl choline ratio was also significantly decreased in Se- pups, implying impaired function of pulmonary surfactant. These data indicate that adequate Se nutrition is important in the maturation of neonatal rat lungs.

• Neonatal Medicine
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• v.15 no.2
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• pp.113-118
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• 2008

Clinical trials in neonates of different gestational age, birth weight, postnatal age and general health status are needed to assure safe and optimal evidence-based-therapy to this special population. Pharmacodynamic maturation must be considered in grouping the neonates for clinical trials. Informed consent from the parents, protection of the neonates participating in the clinical trials, adherence to good clinical practice guidelines, and designation of short term and long term outcomes must be taken into consideration from the beginning of the trials. Collaboration between centers will be helpful in overcoming the problem with small patient size. Many of these challenges are surmountable and an well-designed clinical trial will improve the mortality and morbidity in these very small children.

• Toxicological Research
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• v.16 no.3
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• pp.229-238
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• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.63-68
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• 2017

Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.