• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제22권2호
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• pp.171-180
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• 2019

Purpose: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. Methods: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. Results: All parameters of neurocognitive development and serum calcium ($9.6{\pm}0.9mg/dL$ vs. $10.4{\pm}0.3mg/dL$, p<0.05) and magnesium ($2.02{\pm}0.27mg/dL$ vs. $2.2{\pm}0.14mg/dL$, p<0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition ($1.33{\pm}0.22$ vs. $1.18{\pm}0.22$, p<0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p<0.05, r=0.381). Conclusion: Calcium supplementation may improve neurocognitive development in malnourished infants.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.232-237
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• 2022

Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.

• Biomolecules & Therapeutics
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• 제30권4호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.39-48
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• 2023

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED₅₀ of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.601-610
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• 2003

Biotin is a water-soluble vitamin used as a skin conditioning agent and promotes the formation of intercellular lipid layers through increased lipid synthesis, which improves the skin's natural barrier function. The anti-inflammatory effects of biotin have been investigated using in vitro assay models, such as MTT assay, measurements of concentrations of nitric oxide(NO), prostaglandin E2(PGE$_2$), and inhibition rate of 5-lipoxygenase(5-LOX). In comparison with biotin, other plant extracts were tested at the same time which were kudzu vine extract, sage extract, paeonia extract, and dipotassium glycyrrhetinate. Nitric oxide is a signal molecule with functions such as neurotransmission, local vascular relaxation, and anti-inflammation in many physiological and pathological processes. NO can cause apoptosis and necrosis of target cells such as keratinocytes and is generated from L-arginine by nitric oxide synthase (NOS). Prostanoids, including prostaglandins and thromboxanes, are generated by the phospholipase $A_2$/cyclooxygenase(COX) pathway, and leukotrienes are generated by the 5-lipoxygenase pathway from arachidonic acid. Prostaglandin E2 recently have been shown to be beneficial in the resolution of tissue injury and inflammation, also has been implicated as an immunosuppressive agent and plasma levels of PGE$_2$ are elevated in patients sustaining thermal injury. Lipoxygenase metabolites from arachidonic acid have been implicated in inflammation, anti-inflammatory activity of the raw materials was evaluated in vitro by the offered inhibition of lipoxygenase.

• 한국식품과학회지
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• 제49권2호
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• pp.222-227
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• 2017

본 연구에서는 금 나노입자 용액을 생장하는 6년근 인삼에 직접 시비해서 금 나노입자가 전이된 황금인삼을 열수 추출하여 총페놀 함량, 총플라보노이드 함량, 산화방지능 및 신경세포 보호능을 평가하였다. $1^{\circ}Bx$의 황금홍삼 추출물은 총페놀과 총플라보노이드 함량이 각각 212.2 mg GAE와 3.5 mg CE였다. ABTS, DPPH 및 ORAC 법으로 측정시, 황금홍삼 추출물의 산화방지능은 각각 272.3, 141.2, $868.4mg\;VCE/^{\circ}Bx$였다. 황금홍삼 추출물은 과산화수소로부터 유래한 세포 내 산화스트레스를 감소시켜 PC-12 신경세포의 생존율을 농도 의존적으로 증가시켰다. 또한, 황금홍삼 추출물은 신경전달물질인 아세틸콜린을 가수분해하는 AChE 및 BChE 활성을 억제하였다. 이러한 결과는 금 나노입자를 처리한 홍삼을 이용한 산화방지 및 신경손상억제 소재로 활용할 가능성을 제시하였다.

• 생물정신의학
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• 제6권2호
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• pp.170-175
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• 1999

가족연구, 쌍생아연구, 양자연구 등은 정신분열병의 발생에 유전적 원인이 작용하고 있음을 보여주고 있으며, 생화학적 연구들은 도파민이 중요한 역할을 하는 것으로 보고하고 있다. 한편, tyrosine hydroxylase(TH)는 도파민의 생성에 속도제한효소로 중요한 작용한다. 따라서 본 연구에서는 TH의 유전적 다형성과 정신분열병의 발생, 임상아형 등과의 관련연구를 시행하였다. 환자군은 가톨릭대학교 강남성모병원에 입원하였던 환자중 정신장애 진단 및 통계를 위한 편람 III-R의 진단기준에 의하여 정신분열병으로 진단된 환자로 신경과 질환이나 다른 정신과적 질환이 없는 374명을 대상으로 하였으며, 대조군은 강남성모병원에서 근무하는 직원, 가톨릭대학교 의과대학생, 그리고 강남성모병원 건강진단센터를 방문한 사람중 지원자를 대상으로 하여 393명을 포함하였다. TH 대립유전자의 분포는 환자군과 대조군 사이에 유의한 차이를 보이지 않았으나, 환자군에서는 양성군인 경우 대립유전자 A형의 빈도가 음성군에 비해 높은 것으로 나타났다. 또한 대립유전자 A형을 가지고 있는 환자군은 A형을 가지고 있지 않은 환자군 보다 유의하게 양성증상점수가 높은 것으로 나타났다. 이상의 결과들은 정신분열병의 양성증상과 TH 대립유전자 A형이 관련되어 있음을 시사해 준다고 하겠다.

• 생물정신의학
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• 제4권1호
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• pp.102-107
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• 1997

홍삼사포닌분획의 항불안작용의 양상을 검색하고자 사포닌분획을 사용하여 실험 동물에서 항불안작용을 검색하고 이들의 작용을 benzodiazepine의 대표적 약물인 diazepam의 효과와 비교하여 보았다. 실험동물에서 항불안효과의 검정을 위하여 생쥐에게 각각 상이 한 단일성분 함량을 지닌 여러분획들을 투여 후 elevated plus maze법을 사용하여 항불안효과를 비교, 관찰하였다. 실험결과 홍삼 ginsenoside Rg1, Rf 및 Re 등의 함량이 보다 높은 TSI 분획에서 항불안 효과를 관찰하였다. 중추신경계에 작용하여 진정효과를 나타내는 약물 중 특히 항불안제의 작용에 관여하는 신경전달물질 수용체로 현재까지 가장 주목을 받고 있는 것은 GABA A-benzodiazepine 수용체-chloride통로 복합체에 있는 benzodiazepine 수용체이다. 본 실험결과 관찰한 홍삼 사포닌의 항불안작용의 기전 규명을 위한 접근방법으로 홍삼 사포닌의 benzodiazepine 수용체에 대한 수용체 결합력을 관찰하고자, 흰쥐의 대뇌 피질을 검체로 하여 benzodiazepine 수용체에 대한 [$^3H$] Ro15-1788 결합 실험을 실시하였다. 홍삼 사포닌 분획들은 benzodiazpine 수용체에 결합하는 반응성을 보였으며, ginsenoside Rb, Re 및 Rd등의 함량이 높은 TSIV 분획이 가장 높은 결합력을 나타내었는데, 이 분획에서는 항불안 작용을 관찰할 수 없었다. 이상의 결과에서 볼 때 홍삼사포닌은 항불안작용을 나타내었으며, 이 항불안작용과 benzodiazepine 수용체에 대한 결합력과의 연관성은 관찰되지 않았다.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.252-259
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• 2016

Neuropathic pain is a complex state showing increased pain response with dysfunctional inhibitory neurotransmission. The TREK family, one of the two pore domain $K^+$ (K2P) channel subgroups were focused among various mechanisms of neuropathic pain. These channels influence neuronal excitability and are thought to be related in mechano/thermosensation. However, only a little is known about the expression and role of TREK-1 and TREK-2, in neuropathic pain. It is performed to know whether TREK-1 and/or 2 are positively related in dorsal root ganglion (DRG) of a mouse neuropathic pain model, the chronic constriction injury (CCI) model. Following this purpose, Reverse Transcription Polymerase Chain Reaction (RT-PCR) and western blot analyses were performed using mouse DRG of CCI model and compared to the sham surgery group. Immunofluorescence staining of isolectin-B4 (IB4) and TREK were performed. Electrophysiological recordings of single channel currents were analyzed to obtain the information about the channel. Interactions with known TREK activators were tested to confirm the expression. While both TREK-1 and TREK-2 mRNA were significantly overexpressed in DRG of CCI mice, only TREK-1 showed significant increase (~9 fold) in western blot analysis. The TREK-1-like channel recorded in DRG neurons of the CCI mouse showed similar current-voltage relationship and conductance to TREK-1. It was easily activated by low pH solution (pH 6.3), negative pressure, and riluzole. Immunofluorescence images showed the expression of TREK-1 was stronger compared to TREK-2 on IB4 positive neurons. These results suggest that modulation of the TREK-1 channel may have beneficial analgesic effects in neuropathic pain patients.

• The Korean Journal of Pain
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• 제29권3호
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• pp.164-171
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• 2016

Background: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.