• Proceedings of the PSK Conference
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• 2000.10a
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• pp.177.1-177.1
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• 2000

• Animal cells and systems
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• v.1 no.2
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• pp.381-388
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• 1997

Glutamate is a putative excitatory neurotransmitter in the central nervous system. The present study utilizing monoclonal antibodies against fixative-modified glutamate analyzed the distribution of glutamate-immunoreactive neuronal elements in the dog basilar pons. The glutamatergic neurons were present throughout the rostrocaudal extent of the basilar pons, predominantly to the medial and ventral subdivisions. Labelled cells were relatively sparse in the midline region of the medial nucleus and most lateral area of the lateral nucleus. The majority of glutamate-immunoreactive neuronal somata in the basilar pons was multipolar-shaped, and the size was in the range of 15-25 ${\mu}$m in diameter. Glutamate-immunoreactive axons and terminals were also observed at specific regions of the basilar pons. These observations provide evidence that this excitatory neural element functions in a multisynaptic pathway involving glutamatergic afferents to the basilar pons, pontocerebellar projection neurons, and the granule cells of the cerebellar cortex.

• Korean Journal of Biological Psychiatry
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• v.17 no.4
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• pp.194-202
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• 2010

Alzheimer's disease(AD) is the most common neurodegenerative disorder and constitutes about two thirds of dementia. Despite a lot of effort to find drugs for AD worldwide, an efficient medicine that can cure AD has not come yet, which is due to the complicated pathogenic pathways and progressively degenerative properties of AD. In its early clinical phase, it is important to find the subtle alterations in synapses responsible for memory because symptoms of AD patients characteristically start with pure impairment of memory. Attempts to find the target synaptic proteins and their pathogenic pathways will be the most powerful alternative strategy for developing AD medicine. Here we review recent progress in deciphering the role of target synaptic proteins related to AD in hippocampal glutamatergic synapses.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.613-617
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• 2001

The present study examined the hypothesis that NMDA, AMPA/Kainate, and metabotropic (mGlu) glutamate receptors contribute to a behavioral stimulation induced by activation of dopamine receptors by comparing responses in apomorphine-induced cage climbing behaviors in mice. MK-801, CNQX, and MCPG were served as the NMDA receptor, AMPA/Kainate receptor, and mGlu receptor antagonist, respectively, to elucidate the glutamatergic modulation in apomorphine-induced eopaminergic activation in mice. Drugs were administered intracerebroventricularly (i.c.v.) into the mouse brain 15 min before the apomorphine treatment (2 mg/kg, s.c.). 1.c.v. injection of MK-801 inhibited the apomorphine-induced cage climbing behavior dose-dependently. However, treatments with CNQX and MCPG did not any significant change in apomorphine-induced cage climbing behavior in mice. These results suggest that stimulation of NMDA type of glutamate receptors could contribute to the dopaminergic sti mutation, but not AMPA/Kainate and mGlu type glutamate receptors.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.210-210
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• 1996

Changs in the glutamatergic nervous system following AF64A injection into lateral ventricle were studied in rats. Rats were treated with the infusion of AF64A (3mM) into lateral ventricle At a week after the infusion of AF64A into lateral ventricle, rats were sacrified and each brain resions was dissected ; striatum, hippocampus and frontal cortex. At these resions, total glutamate and other amino acids levels. [$^3$H]Mk801 binding sites and glutamine synthetase activity were measured using HPLC-ECD, ligand binding assay and enzyme activity assay, respectively. The levels of total glutamate were decreased in striatum, hippocampus and frontal cortex Also, the levels of total glycine and taurine were decreased in all examined regions. Furthermore, the levels of total aspartate and GABA were decreased in both hippocampus and frontal cortex but these didn't alter in striatum. Additionally, the levels of total glutamine were decreased in both striatum and frontal cortex. The u\numbers of [$^3$H]MK801 binding sites were differently dffected in each brain resions ; the decrease in striatum, the increase in frontal cortex and no change in hippocampus Glutamine synthetase activity in striatum was significantly decreased. But, that in both hippocampus and frontal cortex didn't alter These results suggest that changes in the glutamatergic nervous system in three regions are induced by following AF64A injection into lateral ventricle in rats.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.295-301
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• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.79-84
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• 2007

Because synaptic refinement of medial nucleus of trapezoid body (MNTB) - lateral superior olive (LSO) synapses is most active during the first postnatal week and the long term depression (LTD) has been suggested as one of its mechanisms, LTD of MNTB-LSO synapses was investigated in neonatal rat brain stem slices with the whole cell voltage clamp technique. In $Mg^{2+}$ free condition, tetanus (10 stimuli at 10 Hz for 2 min) in the current clamp mode induced a robust LTD of isolated D, L-APV-sensitive postsynaptic currents (PSCs) for more than 30 min ($n=6,\;2.4{\pm}0.4%$ of the control), while isolated CNQX-sensitive PSCs were not suppressed ($n=6,\;95.3{\pm}1.6%$). Tetanus also elicited similar LTD in the isolated GABAergic/glycinergic PSCs ($n=6,\;3.6{\pm}0.5%$) and mixed PSCs (GABAergic/glycinergic/glutamatergic) ($n=4,\;2.2{\pm}0.7%$). However, such a strong LTD was not observed in the mixed PSCs when 10 mM EGTA was added in the internal solution (n=10), indicating that postsynaptic $Ca^{2+}$ rise is needed for the strong LTD. This robust LTD might contribute to the active synaptic refinement occurring during the first postnatal week.

• Archives of Pharmacal Research
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• v.23 no.5
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• pp.488-494
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• 2000

Cerebellar granule and glial cells prepared from 7 day-old rat pups were used to investigate the effects of sub-acute nicotine exposure on the glutamatergic nervous system. These cells were exposed to nicotine in various concentrations for 2 to 10 days in situ. Nicotine-exposure did not result in any changes in cerebellar granule and glial cell viability at concentrations of up to 500 $\mu\textrm{M}$. In cerebellar granule cells, the basal extracellular levels of glutamate, aspartate and glycine were enhanced in the nicotine-exposed granule cells. In addition, the responses of N-methyl-D-aspartate (NMDA)-induced glutamate release were enhanced at low NMDA concentrations in the nicotine-exposed granule cells. However, this decreased at higher NMDA concentrations. The glutaminase activity was increased after nicotine exposure. In cerebellar glial cells, glutamate uptake in the nicotine-exposed glial cells were either increased at low nicotine exposure levels or decreased at higher levels. The inhibition of glutamate uptake by L-trans-pyrollidine-2,4-dicarboxylic acid (PDC) was lower in glial cells exposed to 50 $\mu\textrm{M}$ nicotine. Glutamine synthetase activity was lower in glial cells exposed to 100 or 500 $\mu\textrm{M}$ of nicotine. These results indicate that the properties of cerebellar granule and glial cells may alter after subacute nicotine exposure. Furthermore, they suggest that nicotine exposure during development may modulate glutamatergic nervous activity.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.36-42
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• 1997

To investigate effects of ginseng total saponin (GTS) on the ethylcholine aziridnium ion (AF64A) -induced glutamatergic nervous system, rats were pretreated with the infusion of AF64A (3 nmole) into lateral ventricle and were posttreated with 50 mg/kg of GTS, i.p., for 1 week. Twenty four hours after the last administration, rats were sacrificed and the levels of glutamate and taurine, [$^3$H]dizocilpine ([$^3$H]MK801) binding sites and glutamine synthetase activity were assessed in striatum, hippocampus and frontal cortex. The levels of striatal glutamate after GTS treatment in rats were decreased. And the levels of glutamate were decreased in striatum and frontal cortex and increased in hippocampus by the infusion of AF64A. However, the AF64A-induced changes of glutamate were returned to the control level by the administration of GTS in striatum, frontal cortex and hippocampus. After the infusion of AF64A, the level of taurine was decreased in striatum and increased in hippocampus. GTS administrations in the AF64A-treated rats restored to the control level of taurine in the decreased striatal level of taurine, but not in the elevated level of hippocampal taurine. The specific [$^3$H]MK801 binding sites in hippocampus was significantly decreased but not in striatum and frontal cortex after the administration of AF64A. Although GTS itself did not affect the specific [$^3$H]MK801 binding sites, GTS administrations in the AF64A-treated rats did decrease the binding sites of (\`H)Mk801 in all examined regions. The activities of striatal glutamine synthetase were decreased after GTS treatment. The activities of striatal glutamine synthetase (GS) were decreased in AF64A-treated groups. However, the decreased striatal GS activities by AF64A were returned to the control level by GTS treatment. Furthermore, GTS administrations in the AF64A-treated rats increased the hippocampal GS activities. The results indicatethat GTS may adjust the levels of glutamate and taurine constantly and may induce increase in AF64A-induced decrease of GS activity. Thus, it suggests that GTS may antagonize changes in central glutamatergic nervous system induced by AF64A. Also it suggests that the actions of GTS may differently affect in the disease state.