• Title/Summary/Keyword: ${\gamma}-aminobutyric$ acid

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Morus Nigra Extract Attenuates Cognition Impairment and GABAergic Interneuron Degeneration in Aged Rat Brain

  • Lee, Joo Hee;Kim, Yoonju;Song, Min Kyung;Kim, Youn-Jung
    • Journal of Korean Biological Nursing Science
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    • v.24 no.2
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    • pp.77-85
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    • 2022
  • Purpose: Aging process comes with cognitive impairment due to decreased neuronal cell number, activity, and neuronal circuit. Alteration of inhibitory neurons contributes to cognitive impairment in normal aging and is responsible for disrupting the excitation/inhibition balance by reducing the synthesis of gamma-aminobutyric acid (GABA). Morus nigra (Mulberry) is a natural physiologically active substance that has been proven to have anti-oxidant, anti-diabetic, and anti-inflammatory effects through many studies. This study aimed to evaluate the effects of the mulberry extract (ME) on cognitive function through anti-oxidant enzyme and GABAergic neuronal activity in aged rat brain. Methods: Sprague Dawley rats were randomly assigned as the young group (8 weeks, n= 8), aging group (67 weeks, n= 8), and aging+ mulberry extract group (67 weeks, n= 8). The aging+ mulberry extract group was orally administered 500 mg/kg/d mulberry extract for 6 weeks. Results: The aging+ mulberry extract group improved spatial and short-term memory. The antioxidant potential of ME increased the expression of superoxide dismutase-1 (SOD-1) and decreased inducible nitric oxide synthase (iNOS). Also, the aging+ mulberry extract group significantly increased the expression of GABAergic interneuron in hippocampus cornu ammonis1 (CA1) compared to the aging group. Conclusion: The number of GABAergic inhibitory interneurons was deceased and memory functions in the aging process, but those symptoms were improved and restored by mulberry extract administration.

Effects of the Mixed Fermentation of Torulaspora delbrueckii and Saccharomyces cerevisiae on the Non-Volatile and Volatile Compounds and the Antioxidant Activity in Golden Dried Longan Wine

  • Sanoppa, Kanokchan;Huang, Tzou-Chi;Wu, Ming-Chang
    • Microbiology and Biotechnology Letters
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    • v.48 no.1
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    • pp.1-11
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    • 2020
  • The aim of this study was to investigate the effects of Torulaspora delbrueckii and Saccharomyces cerevisiae, as pure fermenters and mixed fermenters (simultaneous and sequential culture), on the production of non-volatiles and volatiles, and on the antioxidant activity in Golden Dried Longan juice and Golden Dried Longan wines. Alanine, arginine, glutamic acid, leucine, proline, and gamma-aminobutyric acid (GABA) were the most prominent amino acids that were found in these wines. The Golden Dried Longan Wine fermented with monocultures of S. cerevisiae and T. delbrueckii produced a total volatile aroma content of 393.21 mg/l and 383.20 mg/l, respectively. Simultaneous culture of the two organisms produced the highest total volatile aroma content, that affected most volatile compounds including isobutanol, ethyl acetate, ethyl decanoate, ethyl heptanoate, ethyl hexanoate, ethyl pentanoate, isoamyl acetate, and isobutyl acetate. Of the four treatments, the sequential culture possessed the highest total phenolic content (5.80 mg gallic acid equivalents (GAE)/ml). In addition, the total phenolic content significantly correlated with the antioxidant activity of the Golden Dried Juice and Golden Dried Longan Wine. These results suggest that co-cultures of the two organisms used in the production of the Golden Dried Longan Wine may improve the intensity and complexity of its aroma.

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
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    • v.19 no.6
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    • pp.523-531
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    • 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.

Central Involvement of Benzodiazepine Receptor on the Muscimol-induced Inhibition of Micturition Reflex in Rats (흰쥐의 뮤시몰투여에 의한 배뇨반사억제효과에 대한 벤조디아제핀수용체의 영향)

  • Huh, In-Hoi;Oh, Ho-Jung
    • YAKHAK HOEJI
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    • v.36 no.5
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    • pp.496-505
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    • 1992
  • The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.

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Physicochemical Properties and Antioxidant Activities of Kimchi-added Croquette (김치 첨가 크로켓의 이화학적 품질 특성 및 항산화 활성)

  • Kim, Taejoon;Surh, Jeonghee
    • Journal of the East Asian Society of Dietary Life
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    • v.26 no.6
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    • pp.498-506
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    • 2016
  • A croquette added with heat-treated kimchi at 20% showing higher sensory preferences was analyzed for its physicochemical properties and antioxidant activity using a croquette without kimchi as a control. Compared with the control, kimchi-added croquette had 3.3-fold higher organic acids content (p<0.001), resulting in a significant reduction of pH (p<0.001) and higher metal chelating activity (p<0.001). Upon addition of kimchi, total reducing capacity increased from 109.4 to $139.4{\mu}g/g$ gallic acid equivalents (p<0.01), and DPPH radical scavenging activity also increased 2-fold, which corresponded to 54% of the electron-donating ability of 0.35 mM gallic acid. In addition, contents of free amino acids and ${\gamma}-aminobutyric$ acid (GABA) appreciably increased by 1.6-fold (p<0.01) and 10-fold (p<0.001), respectively. This could be attributed to the ingredients of kimchi and/or enzymatic transformation of precursors by microorganisms during kimchi fermentation. Kimchi-added croquette was determined to be a good source of dietary fiber relative to its calorie content. Texture profile analysis showed no significant differences in hardness, springiness, cohesiveness, gumminess, and chewiness between the two croquettes with or without kimchi. Taken together, this study shows that utilization of heat-treated kimchi as a filling for croquette could be a good strategy to improve both the nutritional quality and antioxidant activity of croquette.

Maternal separation in mice leads to anxiety-like/aggressive behavior and increases immunoreactivity for glutamic acid decarboxylase and parvalbumin in the adolescence ventral hippocampus

  • Eu-Gene Kim;Wonseok Chang;SangYep Shin;Anjana Silwal Adhikari;Geun Hee Seol;Dae-Yong Song;Sun Seek Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.1
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    • pp.113-125
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    • 2023
  • It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

Effect of Lidocaine on the Release, Receptor Binding and Uptake of Amino Acid Neurotransmitters In vitro (Lidocaine이 아미노산 신경전도물질의 유리, 수용체 결합, 및 섭취에 미치는 효과에 관한 시험관내 실험에 관한 연구)

  • Oh, An-Min;Cheong, Dong-Kyun;Mori, Masakazu
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.17-29
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    • 1988
  • The author examined the effects of lidocaine on the veratrine-or potassium-induced release of neurotransmitters to determine the possible role of amino acid neurotransmitters in lidocaine-induced convulsion. The examined transmitters were gamma-aminobutyric acid (GABA), aspartic acid, glutamic acid and norepinephrine which are released from the synaptosomes. Furthermore, the effects of lidocaine on the binding to receptors and synaptosomal uptake of the two transmitters, GABA and glutamic acid, were determined in crude synaptic membranes and synaptosomes. In addition, the effects of propranolol, norepinephrine and serotonin on the release of amino acid neurotransmitters were also examined. The veratrine-induced release of GABA was most severely inhibited by lidocaine and propranolol, while norepinephrine and serotonin reduced the release of aspartic acid and glutamic acid more than the GABA release. Generally the potassium-induced release was much more resistant to the lidocaine action than the veratrine-induced release. Among the neurotransmitters examined, the aspartic acid release was most prone to the lidocaine action, while the GABA release was most resistant. Concentrations of lidocaine below 1 mM did not significantly change the GABA and glutamic acid receptor binding and uptake. These results indicate that the blocking of sodium channels by lidocaine can result in the selective depression of the GABA release. This may result in unlimited excitation of the central nervous system.

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Modulation of $GABA_A$ Receptor by Protein Kinase C in Autonomic Major Pelvic Ganglion Neurons

  • Choi, Yeun-Jong;Cha, Seung-Kyu;Kim, Dae-Ran;Kong, In-Deok
    • Biomedical Science Letters
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    • v.14 no.2
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    • pp.69-76
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    • 2008
  • ${\gamma}$-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and its actions are mediated by subtypes of GABA receptors named as $GABA_A$, $GABA_B,\;and\;GABA_C,\;GABA_A$, receptor consisting of ${\alpha},\;{\beta},\;{\gamma}\;and\;{\delta}$ subunits is a heterooligomeric ligand-gated chloride channel. This study was performed to investigate regulation of $GABA_A$ receptor by protein kinase C(PKC). Ion currents were recorded using gramicidine-perforated patch and whole cell patch clamp. mRNA encoding the subunits of PKC expressed in major pelvic ganglion (MPG) neurons was detected by using RT-PCR. The GABA-induced inward current was increased by PKC activators and decreased by PKC inhibitors, respectively. These effects were not associated with intracellular $Ca^{2+}$ and GAG (1-oleoyl-2-acetyl-sn-glycerol), a membrane permeable diacylglycerol (DAG) analogue. These results mean that the subfamily of PKC participating in activation of $GABA_A$ receptor would be an atypical PKC (aPKC). Among theses, ${\xi}$ isoform of aPKC was detected by RT-PCR. Taking together, we suggest that excitable $GABA_A$ receptor in sympathetic MPG neuron seemed to be regulated by aPKC, particular in ${\xi}$ isoform. The regulatory roles of PKC on excitatory $GABA_A$ receptors in sympathetic neurons of MPG may be an important factor to control the functional activity of various pelvic organs such as bowel movement, micturition and erection.

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Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABAA Receptor Cl- Channel Activation

  • Ma, Yuan;Ma, Hong;Jo, Young-Jun;Kim, Dong-Seon;Woo, Sung-Sick;Li, Rihua;Hong, Jin-Tae;Moon, Dong-Cheul;Oh, Ki-Wan;Eun, Jae-Soon
    • Biomolecules & Therapeutics
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    • v.16 no.4
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    • pp.328-335
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    • 2008
  • This study was undertaken to investigate whether honokiol could enhance the pentobarbitalinduced sleeping behaviors through $\gamma$-aminobutyric acid (GABA) receptor $Cl^-$ channel activation. Thirty minutes after the oral administration of honokiol, mice were received sodium pentobarbital (42 mg/kg, i.p.). The time elapsed from pentobarbital injection to the loss of the righting reflex was taken as sleeping latency. The time elapsed between the loss and voluntary recovery of the righting reflex was considered as the total sleeping time. Western blot technique and $Cl^-$ sensitive fluorescence probe were used to detect the expression of $GABA_A$ receptor subunits and $Cl^-$ influx in the primary cultured cerebellar granule cells. Honokiol (0.1 and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg) in a dosage-dependent manner. Honokiol (20 and 50 ${\mu}M$) increased $Cl^-$ influx in primary cultured cerebellar granule cells, and selectively increased the $GABA_A$ receptor $\alpha$-subunit expression, but had no effect on the abundance of $\beta$ or $\gamma$-subunits. Chronic treatment with 20 ${\mu}M$ honokiol in primary cultured cerebellar neurons did not affect the abundance of GAD65/67. The results suggested that honokiol could potentiate pentobarbital-induced sleeping through $GABA_A$ receptor $Cl^-$ channel activation.

Effect of Fermentation Time on the Chemical Composition of Mulberry (Morus alba L.) Leaf Teas (발효시간이 뽕잎차 구성성분에 미치는 효과)

  • Bae, Hui-Ae;Baek, Hyeon;Park, Hae-Il;Choung, Myoung-Gun;Sohn, Eun-Hwa;Kim, Sam-Hyun;Kim, Dae-Su;Chung, Ill-Min;Seong, Eun-Soo;Yu, Chang-Yeon;Lim, Jung-Dae
    • Korean Journal of Medicinal Crop Science
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    • v.19 no.4
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    • pp.276-286
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    • 2011
  • Morus alba (Mulberry) leaves were exposed to fermentation for varying amounts of time: no fermentation (0 min, MANF), medial fermentation (10 h, MAMF), and full fermentation (24 h, MAFF). The chemical compositions of the teas were determined and compared with those of commercial Camellia sinensis teas. The results showed that mulberry leaf teas contained significantly higher amounts of ash and fat than Camellia sinensis tea. Compared with Camellia sinensis teas, all mulberry leaf teas contained significantly more total free amino acids (24.26~54.25mg L-glutamic acid equivalent $g^{-1}$), but the concentration of caffeine was relatively low for mulberry leaf teas. High thiamine, riboflavin, and niacin contents were found in all mulberry leaf teas, but ascorbic acid and pyridoxine were found at higher levels in Camellia sinensis teas than in mulberry leaf teas. Color measurements demonstrated that mulberry leaf tea infusions generally had lower $a^*$ (greenness) and $b^*$ (yellowness) values than Camellia sinensis tea infusions. All infusions exhibited low turbidity levels (less than 10%). The contents of total phenols were measured as 71.8 and 74.9mg 100 $ml^{-1}$ infusion in MANF and MAFF, respectively, but the MAMF tea infusion showed significantly lower total phenols (64.6mg 100$ml^{-1}$ infusion). The total flavonoid contents of mulberry leaf tea infusions were lower (8.9~20.6mg 100 $ml^{-1}$ infusion) than those of Camellia sinensis teas and thus had lower antioxidant capacities (DPPH: 326.8~526.9 ${\mu}M$ trolox equivalent $g^{-1}$ and FRAP: 364.6~387.6 ${\mu}M$ trolox equivalent $g^{-1}$) than Camellia sinensis teas. The amounts of ${\gamma}$-aminobutyric acid (GABA) and rutin were higher in fermented mulberry leaf teas; the level of GABA increased with increasing fermentation time and the content was highest in MAFF, but rutin content was highest in MAMF.