• Journal of The Korean Society of Clinical Toxicology
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• v.19 no.2
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• pp.100-109
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• 2021

Purpose: The purpose of this study was to investigate effect of N-acetylcysteine (NAC) on the injury of putative parvalbumin positive interneurons defined by molecular marker and hippocampal long-term potentiation (LTP), a marker of neural plasticity following acute carbon monoxide (CO) poisoning. Methods: Adult Sprague-Dawley rats were exposed to 1100 ppm CO for 40 minutes followed by 3000 ppm CO for 20 minutes. Animals received daily intraperitoneal injection of NAC (150 mg/kg) for 5 days after CO exposure. Changes in learning and spatial memory were evaluated by Y-maze test 5 days after the poisoning. In vivo LTP in hippocampal CA1 area was evaluated by using extracellular electrophysiological technique. Immunohistochemical staining were adopted to observe expressional damages of parvalbumin (PV) immunoreactive interneurons in the hippocampus following the poisoning. Results: Acute CO intoxication resulted in no changes in memory performance at Y-maze test but a significant reduction of LTP in the in hippocampal CA1 area. There was also a significant reduction of PV (+) interneurons in the hippocampal CA1 area 5 days after CO poisoning. Daily treatment of NAC significantly improved hippocampal LTP impairment and reduced immunoreactivity for PV in the hippocampus following the acute CO poisoning. Conclusion: The results of this study suggest that reduction of hippocampal LTP and PV (+) interneurons in the hippocampus is sensitive indicator for brain injury and daily NAC injections can be the alternative therapeutics for the injury induced by acute CO poisoning.

• Journal of Life Science
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• v.27 no.3
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• pp.355-360
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• 2017

Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. This incoordination of blackout may be a major cause in various social problems in alcohol consumption. However, there is still no treatment for preventing these alcohol-induced problems. Hydrangeae dulcis folium is a drug or a tea which is made from the fermented and dried leaves of Hydrangea serrata Seringe. The present study, we tested the ethanol extract of the Hydrangeae dulcis folium (EHDF) on ethanol-induced psychological deficits. To test behavioral deficits, an object recognition test was conducted using a mouse model. To evaluate synaptic deficits, N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential EPSP and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. In the tests, ethanol (1 g/kg, i.p.) impaired object recognition memory, but EHDF (10 or 30 mg/kg) prevented this impairment in object recognition test. Interestingly, EHDF ($30{\mu}g/ml$) significantly ameliorated ethanol-induced LTP and NMDA receptor-mediated synaptic transmission in the hippocampal slices. EHDF prevented ethanol-induced object recognition memory deficits induced by ethanol. Interestingly, EHDF significantly ameliorated ethanol-induced LTP and NMDA receptor- mediated synaptic transmission in the hippocampal slices.

• Journal of Life Science
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• v.29 no.5
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• pp.564-569
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• 2019

Heavy drinking disrupts the nervous system by activation of GABA receptors and inhibition of glutamate receptors, thereby preventing short-term memory formation. Degradation of cognition by alcohol induces blackouts, and it can lead to alcoholic dementia if repeated. Therefore, drugs need to be developed to prevent alcohol-induced blackout. In this study, we confirmed the effect of an ethanol extract of Cassia obtusifolia seeds (COE) on alcohol-induced memory impairment. The effects of COE and ethanol on cognitive functions mice were examined using the passive avoidance and Y-maze tests. The manner in which alcohol affects long-term potentiation (LTP) in relation to the learning and memory was confirmed by electrophysiology performed on mouse hippocampal slices. We also measured N-methyl-D-aspartate (NMDA) receptor-mediated field excitatory synapses (fEPSPs), which have a known association with cognitive impairment caused by ethanol. Ethanol caused memory impairments in passive avoidance and Y-maze tests. COE prevented these ethanol-induced memory impairments in these tests. Ethanol also blocked LTP induction in the mouse hippocampus, and COE prevented this ethanol-induced LTP deficit. Ethanol decreased NMDA receptor-mediated fEPSPs in the mouse hippocampus, and this decrease was prevented by COE. These results suggest that COE might be useful in preventing alcohol-induced neurological dysfunctions, including blackouts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.6
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• pp.356-362
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• 2019

Scutellaria baicalensis (SB) has widely used in the treatment for various brain diseases in the field of Oriental medicine. Biofermantation of SB can make major chemical constituents of SB to pass blood-brain barrier easily and to have more potent anti-oxidant ability. There is a little information about the contribution of fermented SB (FSB) to the formation or maintenance of the neural plasticity in the hippocampus. The purpose of this study was to evaluate effects of FSB extract on hydrogen peroxide (H₂O₂) - induced impairments of the induction and maintenance of long-term potentiation (LTP), an electrophysiological marker for the neural plasticity in the hippocampus. From hippocampal slices of rats, the field excitatory postsynaptic potentials (fEPSPs) were evoked by the electrical stimulation to the Schaffer collaterals - commissural fibers in the CA1 areas and LTP by theta-burst stimulation by using 64 - channels in vitro multi-extracellular recording system. In order to induce oxidative stress to hippocampal slices two different concentrations (200, 400 μM) of H₂O₂ were given to the perfused aCSF before and after the LTP induction, respectively. The ethanol extract of FBS with concentration of 25 ㎍/ml, 50 ㎍/ml was diluted in perfused aCSF that had 200 μM H₂O₂, respectively. Oxidative stress by the treatment of H₂O₂ resulted in decrease of the induction rate of LTP in the CA1 area with a dose - dependent manner. However, the ethanol extract of FSB prevented the reduction of the induction rate of LTP caused by H₂O₂ - induced oxidative stress with a dose - dependent manner. These results may support a potential application of FSB to ameliorate impairments of hippocampal dependent neural plasticity or memory caused by oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.113-119
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• 2002

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is often associated with increases in quantal size, traditionally attributed to enhanced availability or efficacy of postsynaptic glutamate receptors. However, augmented quantal size might also reflect increases in neurotransmitter concentration within the synaptic cleft since AMPA-type glutamate receptors are not generally saturated during basal transmission. Here we report evidence that peak cleft glutamate concentration $([glu]_{cleft})$ increases during LTP, as indicated by a lessening of the blocking effects of rapidly unbinding antagonists of AMPA. The efficacy of slowly equilibrating antagonists remained unchanged. The elevated $[glu]_{cleft}$ helps support the increased quantal amplitude of AMPA-type EPSCs (excitatory postsynaptic currents) during LTP.

• The Journal of Korean Physical Therapy
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• v.13 no.1
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• pp.229-235
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• 2001

Clinical interest has lately been roused by evidence that comprehension of synaptic plasticity may be based on the theoretical opinion. This paper describes perception of synaptic plasticity. Especially processes of long term potentiation(LTP) and long term depression(LTD) are discussed. Recently, it is assessed to genetical parts from development of molecular biology. Therefore this review also represents aspect of molecular events of synaptic plasticity.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.5
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• pp.337-343
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• 2010

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT ($10{\mu}M$) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-$HT_2$ receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-$HT_2$ receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.131-136
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• 2020

Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.2
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• pp.59-65
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• 2022

Rodent model for chronic cerebral hypoperfusion caused by bilateral carotid artery occlusion (BCAO) show clinically relevant evidences for vascular dementia and impairments of synaptic plasticity in the hippocampus. The purpose of this study was to evaluate effect of fermented garlic (F-Garlic) extract with NO metabolites on cognitive behaviors, synaptic plasticity, and molecular events in the hippocampus following BCAO. Adult male Sprague-Dawley rats were randomly divided three experimental groups into: control+water; BCAO+water; BCAO+F-Garlic. Animals were treated with oral administration of F-Garlic in tap water as a drinking water after surgery for 4 weeks. On passive avoidance test and Y-maze test, BCAO+water showed a significant decrease in step-through latency and spontaneous alteration, indicating deficit of hippocampal memory formation but the treatment of F-Garlic significantly increased these cognitive behaviors. In control+water, a robust increase in the amplitude of evoked field excitatory postsynaptic potentials was observed by theta burst stimulation to hippocampal neural circuit indicating formation of long-term potentiation (LTP) in the hippocampal CA1. BCAO+water showed a highly significant deficit in LTP induction 4 weeks after BCAO. On other hand, daily oral administration of F-Garlic extract caused the marked preservation of LTP induction. Moreover, parvalbumin was markedly reduced in the CA1, especially, in the stratum radiatum of BCAO+water. In contrast, BCAO+F-Garlic mitigate a significantly reduction of the parvalbumin. In summary, these results suggest that daily oral administration of F-Garlic extract can ameliorate cognitive memory deficit through the preservation of synaptic plasticity and interneurons integrity in the hippocampus in rodent model of chronic cerebral hypoperfusion.