• 제목/요약/키워드: GABAA

검색결과 18건 처리시간 0.03초

지치 유래 naphthoquinone을 전처치한 생쥐에서 우울 및 불안 조절 효과 (The effect of pretreated Lithospermum erythrorhizon derived-naphthoquinone on anxiety, depression in mice)

  • 제현동;민영실
    • 융합정보논문지
    • /
    • 제10권7호
    • /
    • pp.116-121
    • /
    • 2020
  • 본 연구는 불안, 불면증, 우울증 또는 삶의 질에 대하여 지치(Lithospermum erythrorhizon) 유래 naphthoquinone, 즉 shikonin의 영향을 고찰하고, 확실히 밝혀지지 않은 메카니즘을 규명하고자한다. 우리는 지치의 주요성분인 naphthoquinone이 스트레스에 의한 수면장애, 강제수영에 의한 우울, 미로에 의해 유발된 불안현상 등의 조절에 영향을 미칠 것이라고 가설을 세웠다. 수컷 쥐를 이용하여 부동 혹은 수영시간, 수면시간, open arms으로 지속시간 및 진입빈도를 측정하고 기록하였다. Naphthoquinone(10, 30 & 100mg/kg)의 투여군에서 GABAA receptor의 활성으로 일어나는 barbiturate-유도 수면을 증가시켰다. 미로에서 open arms 상태로 지속되는 시간이 증가되고, 강제수영에서 부동시간이 줄었다. 결과적으로 naphthoquinone은 불안을 완화, 수면과 항우울경향이 있고, 불안, 불면과 우울증에서 효과적인 치료효과가 있었다.

GABA 수용체 영상 (GABA Receptor Imaging)

  • 이종두
    • Nuclear Medicine and Molecular Imaging
    • /
    • 제41권2호
    • /
    • pp.166-171
    • /
    • 2007
  • GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

Modulation of the Expression of the GABAA Receptor β1 and β3 Subunits by Pretreatment with Quercetin in the KA Model of Epilepsy in Mice -The Effect of Quercetin on GABAA Receptor Beta Subunits-

  • Moghbelinejad, Sahar;Rashvand, Zahra;Khodabandehloo, Fatemeh;Mohammadi, Ghazaleh;Nassiri-Asl, Marjan
    • 대한약침학회지
    • /
    • 제19권2호
    • /
    • pp.163-166
    • /
    • 2016
  • Objectives: Quercetin is a flavonoid and an important dietary constituent of fruits and vegetables. In recent years, several pharmacological activities of quercetin, such as its neuroprotective activity and, more specifically, its anti-convulsant effects in animal models of epilepsy, have been reported. This study evaluated the role of quercetin pretreatment on gene expression of ${\gamma}$-amino butyric acid type A ($GABA_A$) receptor beta subunits in kainic acid (KA)-induced seizures in mice. Methods: The animals were divided into four groups: one saline group, one group in which seizures were induced by using KA (10 mg/kg) without quercetin pretreatment and two groups pretreated with quercetin (50 and 100 mg/kg) prior to seizures being induced by using KA. Next, the messenger ribonucleic acid (mRNA) levels of the $GABA_A$ receptor ${\beta}$ subunits in the hippocampus of each animal were assessed at 2 hours and 7 days after KA administration. Quantitative real-time polymerase chain reaction (RT-PCR) assay was used to detect mRNA content in hippocampal tissues. Results: Pretreatments with quercetin at doses of 50 and 100 mg/kg prevented significant increases in the mRNA levels of the ${\beta}_1$ and the ${\beta}_3$ subunits of the $GABA_A$ receptor at 2 hours after KA injection. Pretreatment with quercetin (100 mg/kg) significantly inhibited ${\beta}_1$ and ${\beta}_3$ gene expression in the hippocampus at 7 days after KA injection. But, this inhibitory effect of quercetin at 50 mg/kg on the mRNA levels of the ${\beta}_3$ subunit of the $GABA_A$ receptor was not observed at 7 days after KA administration. Conclusion: These results suggest that quercetin (100 mg/kg) modulates the expression of the $GABA_A$ receptor ${\beta}_1$ and ${\beta}_3$ subunits in the KA model of epilepsy, most likely to prevent compensatory responses. This may be related to the narrow therapeutic dose range for the anticonvulsant activities of quercetin.

Lactobacillus brevis BJ20를 이용한 굴(Crassostrea gigas).다시마(Saccharina japonica) 발효 분말의 항산화 및 항염증 활성 효과 (Effects of Lactobacillus brevis BJ20 Fermentation on the Antioxidant and Antiinflammatory Activities of Sea Tangle Saccharina japonica and oyster Crassostrea gigas)

  • 강영미;우남식;서용배
    • 한국수산과학회지
    • /
    • 제46권4호
    • /
    • pp.359-364
    • /
    • 2013
  • Inordinate stress causes disorders of various systems in humans and activates defense mechanisms to maintain homeostasis in the body. Sleep is a vital, highly organized process regulated by complex systems of neuronal networks and neurotransmitters. Sleep is an essential biological process whose underlying regulating involves numerous anatomical structures and biochemical substances that can be compromised by stress and by the immune system. Gamma-amino butyric acid (GABA) is the main inhibitory neurotransmitter of the central nervous system, and activation of GABAA receptors is known to favor sleep. This study was conducted to evaluate the possible application of Lactobacillus brevis BJ20 fermentation to improve the functional qualities of sea tangle Saccharina japonica and oyster Crassostrea gigas. Antioxidant activity was determined by assaying levels of radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide. L. brevis BJ20 fermentation of sea tangle and oyster enhanced both antioxidant and antiinflammatory activities. These results suggested that L. brevis BJ20 fermented sea tangle and oyster could be used for alleviation of stress and to promote sleep.

Intraocular Injection of Muscimol Induces Illusory Motion Reversal in Goldfish

  • Lee, Sang-Yoon;Jung, Chang-Sub
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제13권6호
    • /
    • pp.469-473
    • /
    • 2009
  • Induced activation of the gamma-aminobutyric $acid_A$ ($GABA_A$) receptor in the retina of goldfish caused the fish to rotate in the opposite direction to that of the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a $GABA_A$ receptor agonist, modified OMR in a concentration-dependent manner. The $GABA_B$ receptor agonist baclofen and $GABA_C$ receptor agonist CACA did not affect OMR. The observed modifications in OMR included decreased anterograde rotation $(0.01\sim0.03\;{\mu}M)$, coexistence of retrograde rotation and decreased anterograde rotation $(0.1\sim30\;{\mu}M)$ and only retrograde rotation $(100\;{\mu}M\sim1\;mM)$. In contrast, the $GABA_A$ receptor antagonist bicuculline blocked muscimol-induced retrograde rotation. Based on these results, we inferred that the coding inducing retrograde movement of the goldfish retina is essentially associated with the GABAA receptor-related visual pathway. Furthermore, from our novel approach using observations of goldfish behavior the induced discrete snapshot duration was approximately 573 ms when the fish were under the influence of muscimol.

Methanol Extract of Zizyphi Spinosi Semen Augments Pentobarbital-Induced Sleep through the Modification of GABAergic Systems

  • Hu, Zhenzhen;Kim, Chung-Soo;Oh, Eun-Hye;Lee, Mi-Kyung;Eun, Jae-Soon;Hong, Jin-Tae;Oh, Ki-Wan
    • Natural Product Sciences
    • /
    • 제18권2호
    • /
    • pp.67-75
    • /
    • 2012
  • Zizyphi Spinosi Semen (ZSS) have been widely used for the treatment of insomnia in Asia. This experiment was performed to investigate whether methanol extract of ZSS (MEZSS) has hypnotic effects through the ${\gamma}$-amino butyric acid (GABA)ergic systems. MEZSS inhibited the locomotor activity. MEZSS enhanced pentobarbital-induced sleep behaviors. However, MEZSS itself did not induce sleep at higher dose, similar to muscimol. On the other hand, both pentobarbital and MEZSS increased the non rapid eye move (NREM) sleep, especially reducing the -wave electroencephalogram (EEG) activity in REM sleep. MEZSS showed similar effects with muscimol on potentiating chloride influx induced by pentobarbital. MEZSS significantly increased GABAA receptors ${\gamma}$-subunit expression and slightly decreased ${\beta}$-subunit expression in hypothalamus and thalamus, showing that subunit-expression was similar to diazepam. In addition, MEZSS enhanced the expression of glutamic acid decarboxylase (GAD). In conclusion, it is suggested that MEZSS might augment pentobarbital-induced sleep behaviors through the modification of GABAergic systems.

영신초(靈神草)의 항우울 효과에 대한 행동약리학적 연구 (Studies on the Behavioral Pharmacology of the Antidepressant Effect of Polygala japonica Houtt)

  • 이은경;정대규
    • 동의신경정신과학회지
    • /
    • 제22권2호
    • /
    • pp.129-146
    • /
    • 2011
  • Objectives : The purpose of this study was to characterize the putative antidepressant and antianxiolytic effects of the 70% ethanol extract of Polygala japonica(EEPJ) using animal's behavioral experiment in mice. Methods : The effect of EEPJ on the anxioty and depressive disorder was investigated via mice's behavioral experiment like Elevated plus-maze, Horizontal wire test, Open field test, Forced swimming test, Tail suspension test, and it was happen via any mechanism by WAY 100635, a 5-HT1A receptor antagonist and by Flumazenil, a GABAA antagonist Results : 1. In the EPM, single treatments of the EEPJ(200 and 400mg/kg) had usefully antianxiolytic effects versus vehicle, which was medicated via the serotonergic nervous system. 2. In the HWT, single treatments of the EEPJ were no changes in the myorelaxant effects versus vehicle. 3. In the OFT, single treatments of the EEPJ were no changes in the locomotor activity versus vehicle. 4. In the FST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. 5. In the TST, single treatments of the EEPJ(50mg/kg) significantly reduced the immobility time versus vehicle. Conclusions : These results indicate that EEPJ is an effective antidepressant and antianxiolytic activity in mice, and it might be usefully applied for prevention and treatment of depressive disorder through evolutive study like development of various experimental models.

Enhancement of GluN2B Subunit-Containing NMDA Receptor Underlies Serotonergic Regulation of Long-Term Potentiation after Critical Period in the Rat Visual Cortex

  • Joo, Kayoung;Rhie, Duck-Joo;Jang, Hyun-Jong
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제19권6호
    • /
    • pp.523-531
    • /
    • 2015
  • Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, ${\gamma}$-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network.

4-Hydroxybenzaldehyde, One of Constituents from Gastrodiae Rhizoma Augments Pentobarbital-induced Sleeping Behaviors and Non-rapid Eye Movement (NREM) Sleep in Rodents

  • Choi, Jae Joon;Kim, Young-Shik;Kwon, Yeong Ok;Yoo, Jae Hyeon;Chong, Myong-Soo;Lee, Mi Kyeong;Hong, Jin Tae;Oh, Ki-Wan
    • Natural Product Sciences
    • /
    • 제21권3호
    • /
    • pp.219-225
    • /
    • 2015
  • In the previous experiments, we reported that ethanol extract of Gastrodiae Rhizoma, the dried tuber of Gastrodia ElataBlume (Orchidaceae) increased pentobarbital-induced sleeping behaviors. These experiments were undertaken to know whether 4-hydroxybenzaldehyde (4-HBD), is one of the major compounds of Gastrodiae Rhizoma increases pentobarbital-induced sleeping behaviors and changes sleep architectures via activating GABAA-ergic systems in rodents. 4-HBD decreased locomotor activity in mice. 4-HBD increased total sleep time, and decreased of sleep onset by pentobarbital (28 mg/kg and 40 mg/kg). 4-HBD showed synergistic effects with muscimol (a GABAA receptor agonist), shortening sleep onset and enhancing sleep time on pentobarbital-induced sleeping behaviors. On the other hand, 4-HBD (200 mg/kg, p.o.) itself significantly inhibited the counts of sleepwake cycles, and prolonged total sleep time and non-rapid eye movement (NREM) in rats. Moreover, 4-HBD increased intracellular Cl levels in the primary cultured cerebellar cells. The protein levels of glutamic acid decarboxylase (GAD) and GABAA receptors subunits were over-expressed by 4-HBD. Consequently, these results demonstrate that 4-HBD increased NREM sleep as well as sleeping behaviors via the activation of GABAA-ergic systems in rodents.