• Title/Summary/Keyword: GABA$_A$ receptor

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Benzodiazepine 계열 약물 복용 환자의 수면다원검사에서 도출된 EEG유형 분석 (Polysomnography Analysis of Electroencephalography in Patients Expending Benzodiazepine Drugs)

  • 장다준;임동규;김재경
    • 대한임상검사과학회지
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    • 제53권4호
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    • pp.333-341
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    • 2021
  • 벤조디아제핀은 GABAA 수용체에 작용하고 신경 억제제로 작용하며 불안, 불면증 및 공황 장애를 치료하는 데 사용되는 약물 그룹이다. 우리는 연령, 벤조디아제핀 사용 여부 및 사용 기간에 따라 수면 중 뇌파 소견에 차이가 있는지 관찰하기 위해 30명의 개인의 데이터를 분석했다. 수면다원검사를 통해 얻은 뇌파 소견을 이용하여 벤조디아제핀 복용군과 비복용군, 단기 및 장기복용, 노인과 비 노인군, 고령 단기복용 및 고령 장기복용군을 비교했다. 평가된 항목은 수면 잠복기, 수면 효율, 수면 단계별 백분율, sleep spindle의 개수 및 평균 주파수로 설정하였다. 복용군과 비복용군의 비교에서 sleep stage와 sleep spindle의 평균 주파수 항목에서 유의미하였다. 장기복용과 단기복용군의 비교에서 sleep efficiency 항목에서 유의미하였다. 노인군과 비 노인군과의 비교에서 sleep efficiency, sleep stage 항목에서 유의미하였다. 전반적으로 이 연구 결과를 바탕으로 벤조디아제핀의 사용은 느린 주파수 수면을 억제하고 수면 방추파의 주파수와 빈도를 증가시킨다는 결론을 내릴 수 있다.

Impaired Avoidance Learning and Increased hsp70 mRNA Expression in Pentylenetetrazol-treated Zebrafish

  • Kim, Yeon-Hwa;Lee, Yun-Kyoung;Lee, Han-Sol;Jung, Min-Whan;Lee, Chang-Joong
    • Animal cells and systems
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    • 제13권3호
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    • pp.275-281
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    • 2009
  • The effects of pentylenetetrazol (PTZ), a GABA receptor antagonist, were studied on passive avoidance learning and expression of heat shock protein 70 (hsp70), neuroglobin, and fatty acid binding protein-7 (fabp-7) genes. Zebrafish were trained to stay in a dark compartment to avoid a weight dropping in an acryl shuttle box with a central sliding door. In two training sessions of 2 h interval, each consisting of 3 trials, the crossing time was significantly increased from $43.2{\pm}14.4s$ to $149.3{\pm}38.5s$ in the first training session and remained $116.1{\pm}36.0s$ s in the first trial of the second training session in the control. In zebrafish treated with PTZ before the first training session, the crossing time was significantly increased neither in the first nor in the second training session. However, the increased crossing time was maintained in the second training session when 10 mM PTZ was treated three times for 10 min at 30 min intervals between the first and second training session. Quantitative real-time PCR showed that expression level of hsp70 mRNA increased two to eight fold over that of control in the brain at 0-24 h after termination of PTZ treatment. No change in expression of neuroglobin and fabp-7 mRNA was shown in PTZ-treated zebrafish. Our studies suggest that PTZ impairs learning ability in avoidance response and also modifies expression of genes related to the neuroprotection.

알쯔하이머 질환의 신경생물학 (Neurobiology of Alzheimer's Disease)

  • 정영조;서승우;이승환
    • 생물정신의학
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    • 제8권1호
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    • pp.62-70
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    • 2001
  • Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

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Anxiolytic-like Effects of Polygala tenuifolia Willdenow Using the Elevated Plus Maze and Hole-board Apparatus in Mice

  • Jung, Ji-Wook;Yoon, Byung-Hoon;Kim, Sun-Yeou;Cheong, Jae-Hoon;Ryu, Jong-Hoon
    • Biomolecules & Therapeutics
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    • 제13권2호
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    • pp.84-89
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    • 2005
  • The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.

봉독의 주요성분인 Melittin과 MCDP이 비만세포주에서 유전자 발현에 미치는 영향에 대한 microarray 분석 (cDNA microarray gene expression profiling of melittin and mast cell degranulation peptide in human mast cell strain)

  • 소재진;우현수;김창환
    • Journal of Acupuncture Research
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    • 제22권3호
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    • pp.37-51
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    • 2005
  • 비만세포는 염증 및 알레르기 반응과 관련하여 우리 몸에서 주요한 작용을 하는 세포이다. 봉독은 현재까지 진통기전에 관련된 모델로 연구가 진행되어 왔으나, 최근에는 항염증이나 항알러지반응 둥에서 면역세포와 관련 한 연구가 진행 중에 있다. 본 연구는 봉독의 주요성분인 melittin과 MCD Peptide가 비만세포주에서의 유전자 발현에 미치는 영향을 연구함으로써 향후 유전자 언구에 관련한 기초를 제시하고자 하였다. 본 연구에서는 사람의 비만세포주를 이용하여, 세포독성 실험을 거쳐서 얻은 유효농도에서 각각 melittin과 MCD Peptide를 처치하고, 이때 변화하는 유전자의 발현양상을 microarray분석기법을 통하여 정보를 얻었다. 실험적 통계에 의하여 global M이 1 또는 -1 이상인 것을 유의한 것으로 보았을 때, melittin에서는 모두 7개 의 유전자가 항진되고, 8개의 유전자가 어제되었다. MCDP에서는 7개의 유전자가 항진되고 17개의 유전자가 억제되었다. 이들 유전자들이 주로 관련하는 체내의 작용은 세포내에서 단백결합, lymphocyte 기능의 활성화, macrophage 항원관련 및 세포핵의 수용체, GABA A receptor 관련물질, cAMP 반응요소와 연관된 단백질, 보체계 8번 및 B-cell 관련물질, 다낭성 신질환에 관련된 단백물질, 염증관련물질, 혈액응고에 영향을 주는 단백물질등과 연관이 되었다. 이러한 분석결과를 통하여 동복에서의 주요약리작용을 담당하는 melittin과 MCD peptide의 작용기전을 밝히는데 보다 유용한 자료를 얻을 수 있었으며, 향후에 봉독의 주요성분 및 전체봉 독액이 항알레르기반응이나 항염증작용에 미치는 영향에 대한 심도있는 연구가 필요할 것으로 사료된다.

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Galectin-3-independent Down-regulation of GABABR1 due to Treatment with Korean Herbal Extract HAD-B Reduces Proliferation of Human Colon Cancer Cells

  • Kim, Kyung-Hee;Kwon, Yong-Kyun;Cho, Chong-Kwan;Lee, Yeon-Weol;Lee, So-Hyun;Jang, Sang-Geun;Yoo, Byong-Chul;Yoo, Hwa-Seong
    • 대한약침학회지
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    • 제15권3호
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    • pp.19-30
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    • 2012
  • Objectives: Many efforts have shown multi-oncologic roles of galectin-3 for cell proliferation, angiogenesis, and apoptosis. However, the mechanisms by which galectin-3 is involved in cell proliferation are not yet fully understood, especially in human colon cancer cells. Methods: To cluster genes showing positively or negatively correlated expression with galectin-3, we employed human colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4 and SNU-C5 in high-throughput gene expression profiling. Gene and protein expression levels were determined by using real-time quantitative polymerase chain reaction (PCR) and western blot analysis, respectively. The proliferation rate of human colon cancer cells was measured by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Expression of ${\gamma}$-aminobutyric acid B receptor 1 (GABABR1) showed a positive correlation with galectin-3 at both the transcriptional and the translational levels. Down-regulation of galectin-3 decreased not only GABABR1 expression but also the proliferation rate of human colon cancer cells. However, Korean herbal extract, HangAmDan-B (HAD-B), decreased expression of GABABR1 without any expressional change of galectin-3, and offset ${\gamma}$-aminobutyric acid (GABA)-enhanced human colon cancer cell proliferation. Conclusions: Our present study confirmed that GABABR1 expression was regulated by galectin-3. HAD-B induced galectin-3-independent down-regulation of GABABR1, which resulted in a decreased proliferation of human colon cancer cells. The therapeutic effect of HAD-B for the treatment of human colon cancer needs to be further validated.

복합한약제제의 수면에 대한 연구 -더웰 제제에 대하여- (Study on Sleeping Behaviors of The Combined-Preparation of Crude Drugs -on The $Well^{TM}$ Preparation-)

  • 방금엽;이미경;서승용;전훈;김대근;오기완;조형권;은재순
    • 동의생리병리학회지
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    • 제25권6호
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    • pp.996-999
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    • 2011
  • This experiment was performed to investigate whether the combined-preparation of crude drugs (The $Well^{TM}$ Preparation, TW), has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors. TW was mixed with water extracts of Ginseng Radix red, Germinated brown rice, cultured mountain ginseng, and 50% ethanol extracts of Longanae Arillus, Nelumbinis Folium and Chrysanthemi Flos. TW (100 mg/kg, p.o.) reduced sleep onset and prolonged sleep time induced by pentobarbital similar to muscimol (0.2 ${\mu}M$), a $GABA_A$ receptor agonist. Also, TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) did not affect the chloride influx in primary cultured cerebellar granule cells, respectively, but the combined-treatment of TW (2 ${\mu}g$/ml) and pentobarbital (2.5 ${\mu}M$) increased the chloride influx onto the cells. In conclusion, TW augments pentobarbital-induced sleep behaviors; these effects may result from chloride channel activation.

우울증의 새로운 신경생물학 (The New Neurobiology of Depression)

  • 김용구
    • 생물정신의학
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    • 제8권1호
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    • pp.3-19
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    • 2001
  • Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

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시판소시지의 조리방법 및 재가열이 조직특성에 미치는 영향 (Effect of Cooking Methods and Reheating on Texture of Sausage)

  • 김성희;이숙미;조정순
    • 한국식품영양과학회지
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    • 제26권1호
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    • pp.37-44
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    • 1997
  • 본 실험은 시중에서 판매하는 소시지를 전자렌지(micro-waving), 가스오븐(gas-broiling), 튀김 (frying)으로 조리한 다음, 냉장.저장하였다가 3일째, 6일째에 각 각 재가열하여 관능검사와 조직감 측정을 하였다. 이를 통하여 조리 방법, 냉장.저장 후 재가열에 따른 조직 특성에 대해 연구하여 다음과 같은 결론을 보고하는 바이다. 관능검사결과를 조리 방법 별로 살펴보면 조리 하지 않은 상태의 소시지가 촉촉한 정도, 경도에서 높은 수치를 나타내었으며, 짠맛의 정도는 재가열함에 따라 수치가 높아졌다. 저작성은 전자렌지 조리에서 높은 수치를 보였으나 두 제조회사 제품이 다른 양상을 보였다. 뒷맛은 가스오븐 조리에서 가장 높게 나타났고, 조리하지 않은 상태의 소시지가 뒷맛이 가장 약함을 보였다. 산패취는 다른 조리방법에 비하여 튀김 조리에서 유의하게 높게 나타났다. 조리하여 냉장 저장 한 후 3일째, 6일째 재가열했을 때, 저장 기간이 길어짐 에 따라 경도, 짠맛의 정도, 산패취, 뒷맛의 수치는 증가함을 보였으나 촉촉한 정도, 저작성은 감소함을 보였다. 전반적인 기호도는 전자렌지와 가스오븐으로 조리하여 냉장.저장한 후 3일째 재가열했을 때가 가장 높은 수치를 나타내었다. 기계적인 분석을 하였을 때 튀김조리에서 경도, 뭉침성, 씹힘성이 높은 수치를 나타냈으며, 응집성과 탄력성에서는 조리방법 별로 유의한 차이는 나타내지 않았다. 조리하여 냉장.저장한 후 재가열할 때에는 3일째, 6일째 재가열할수록 경도, 응집성, 탄력성, 뭉침성, 씹힘성이 증가하는 경향을 보였다. 경도, 응집성, 뭉침성, 씹힘성은 가스오븐으로 조리하여 냉장 저장한 후 3일째에 재가열한 소시지에서 유의하게 높았다.우(각각 20.0%), 땅콩 및 콩(각각 16.7%) 등의 순이었다. 연령 대별로는 10대 이하에서는 우유, 20대~30대에서는 복숭아, 40대 이상에서는 돼지고기가 많이 나타났다.ing of [sub 3/H]SR95531 to GABA receptor. Butanol fraction of G. elata significantly diminished the pentylenetetrazole-induced lethality of mice. From these results, it can be concluded that substance or substances with neurochemical properties characteri- stic of a benzodiazepine receptor agonist may be important components, and contribute to the anticonvulsant property of G. elata.clooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is

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GABA-enriched fermented Laminaria japonica improves cognitive impairment and neuroplasticity in scopolamine- and ethanol-induced dementia model mice

  • Reid, Storm N.S.;Ryu, Je-kwang;Kim, Yunsook;Jeon, Byeong Hwan
    • Nutrition Research and Practice
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    • 제12권3호
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    • pp.199-207
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    • 2018
  • BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.