• Title/Summary/Keyword: neuroscience

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Effects of cyanocobalamin and its combination with morphine on neuropathic rats and the relationship between these effects and thrombospondin-4 expression

  • Duzenli, Neslihan;Ulker, Sibel;Sengul, Gulgun;Kayhan, Buse;Onal, Aytul
    • The Korean Journal of Pain
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    • v.35 no.1
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    • pp.66-77
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    • 2022
  • Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone.

Discourse on ICT Virtual Reality Media : Focusing on Immersible Space and Communication Theories (ICT기반 가상현실(VR) 미디어에 대한 담론 :몰입 공간과 소통이론을 중심으로)

  • Kim, Jung Kyu;Kim, Jong Kouk
    • The Journal of the Convergence on Culture Technology
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    • v.7 no.2
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    • pp.333-338
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    • 2021
  • Development of 5th generation mobile telecommunication technology is visualizing ideal hyper-connected social information and communication technology (ICT). In particular, virtual reality (VR) technology is at the starting point for new expansion and leaps. This work defines virtual reality as media in this context and collects and analyzes discourse on its scalability around space and communication theory. We first elaborated the concept, starting with the early discussions of the virtual reality concept in 1990, and discussed the relationship between the physical world and digital information, expression and interaction immersion as a medium, simulation, art creation theory, and finally evolutionary development. In conclusion, beyond the discourse on the technology of virtual reality, academic subjects were required to have theoretical frameworks on cognitive science, neuroscience, social science, and humanities issues (ethics, personality, etc.) for the development and evolution of virtual reality. In other words, it is time for the evolution of virtual reality to be discussed, which can be moved beyond.

Effectiveness of Additional Administration of a Banha-sasim-tang Formulation to Patients with Gastrointestinal Symptoms (KCD K-code) Not Improved by Western Medicines: A Retrospective Chart Review (합성의약품으로 호전되지 않은 소화기 증상 환자(KCD K-코드)에 대한 반하사심탕 제제 병용의 효과 : 후향적 차트 분석)

  • Kim, Cheol-hyun;Kim, Kwangho;Lee, Young-ung;Kang, Sunny;Kang, Geonhui
    • The Journal of Internal Korean Medicine
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    • v.42 no.6
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    • pp.1349-1355
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    • 2021
  • Objectives: The aim of this study was to evaluate the effectiveness of additional administration of Banha-sasim-tang formulation to patients with gastrointestinal symptoms that did not improve with Western medicines. Methods: The patients who met the inclusion and exclusion criteria were analyzed retrospectively. A paired t-test was performed on the Nepean Dyspepsia Index-Korean version (NDI-K) scores before and after administering the Banha-sasim-tang formulation. Results: A total of 27 subjects were included. The mean duration of taking the Banha-sasim-tang formulation was 15.6±3.1 days. The most commonly used Western medicine before taking the Banha-sasim-tang formulation was rebamipide. The means of the NDI-K score were 57.4±21.8 before administering Banha-sasim-tang formulation and 34.9±16.5 after administration, and the difference was statistically significant (p<0.0001). No serious side effects were encountered while taking the Banha-sasim-tang formulation. Conclusions: For patients whose gastrointestinal symptoms do not improve with Western medicines, additional administration of Banha-sasim-tang formulation may be an option. However, as this study is a retrospective chart review, prospective, large-scale, double-blind studies are needed in the future.

Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development

  • Adil, Keremkleroo Jym;Remonde, Chilly Gay;Gonzales, Edson Luck;Boo, Kyung-Jun;Kwon, Kyong Ja;Kim, Dong Hyun;Kim, Hee Jin;Cheong, Jae Hoon;Shin, Chan Young;Jeon, Se Jin
    • Biomolecules & Therapeutics
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    • v.30 no.4
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    • pp.320-327
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    • 2022
  • Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

Transcriptional Regulatory Role of NELL2 in Preproenkephalin Gene Expression

  • Ha, Chang Man;Kim, Dong Hee;Lee, Tae Hwan;Kim, Han Rae;Choi, Jungil;Kim, Yoonju;Kang, Dasol;Park, Jeong Woo;Ojeda, Sergio R.;Jeong, Jin Kwon;Lee, Byung Ju
    • Molecules and Cells
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    • v.45 no.8
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    • pp.537-549
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    • 2022
  • Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

Acceleration of Mesenchymal-to-Epithelial Transition (MET) during Direct Reprogramming Using Natural Compounds

  • Seo, Ji-Hye;Jang, Si Won;Jeon, Young-Joo;Eun, So Young;Hong, Yean Ju;Do, Jeong Tae;Chae, Jung-il;Choi, Hyun Woo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.10
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    • pp.1245-1252
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    • 2022
  • Induced pluripotent stem cells (iPSCs) can be generated from somatic cells using Oct4, Sox2, Klf4, and c-Myc (OSKM). Small molecules can enhance reprogramming. Licochalcone D (LCD), a flavonoid compound present mainly in the roots of Glycyrrhiza inflata, acts on known signaling pathways involved in transcriptional activity and signal transduction, including the PGC1-α and MAPK families. In this study, we demonstrated that LCD improved reprogramming efficiency. LCD-treated iPSCs (LCD-iPSCs) expressed pluripotency-related genes Oct4, Sox2, Nanog, and Prdm14. Moreover, LCD-iPSCs differentiated into all three germ layers in vitro and formed chimeras. The mesenchymal-to-epithelial transition (MET) is critical for somatic cell reprogramming. We found that the expression levels of mesenchymal genes (Snail2 and Twist) decreased and those of epithelial genes (DSP, Cldn3, Crb3, and Ocln) dramatically increased in OR-MEF (OG2+/+/ROSA26+/+) cells treated with LCD for 3 days, indicating that MET effectively occurred in LCD-treated OR-MEF cells. Thus, LCD enhanced the generation of iPSCs from somatic cells by promoting MET at the early stages of reprogramming.

The role of botulinum toxin type A related axon transport in neuropathic pain induced by chronic constriction injury

  • Bu, Huilian;Jiao, Pengfei;Fan, Xiaochong;Gao, Yan;Zhang, Lirong;Guo, Haiming
    • The Korean Journal of Pain
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    • v.35 no.4
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    • pp.391-402
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    • 2022
  • Background: The mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats. Methods: Chronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots. Results: The subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats. Conclusions: BTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.

Modification of Insect Sodium Currents by a Pyrethroid Permethrin and Positive Cooperativity with Scorpion Toxins (피레스로이드계 살충제 퍼메트린이 Heliothis virescens 중추신경세포에 있는 나트륨채널에 작용하는 기작을 전기생리학적으로 연구)

  • Lee, Daewoo;Adams, Michael E.
    • Korean journal of applied entomology
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    • v.61 no.1
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    • pp.117-128
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    • 2022
  • In this study, we have examined pyrethroid actions on sodium channels in the pest insect Heliothis virescens. The synthetic pyrethroid permethrin increased steady-state sodium current in H. virescens central neurons and prolonged tail currents (INa-tail) due to extreme slowing of sodium channel deactivation. Prolongation of INa-tail was evident at permethrin concentrations as low as 60 nM, which modified ~1.7% of sodium channels and 10 μM permethrin modified about 30% of channels. The average time constant (τ1) of tail current decay was ~335 ms for permethrin-modified channels. These modified channels activated at more negative potentials and showed slower activation kinetics, and failed to inactivate. Permethrin modification of sodium channels was dramatically potentiated by the α scorpion toxin LqhαIT, showing positive cooperativity between two binding sites. The amplitude of the tail current induced by 0.3 μM permethrin was enhanced ~8-fold by LqhαIT (200 pM). Positive cooperativity was also observed between permethrin and the insect-specific scorpion toxin AaIT as 10 nM permethrin potentiated the shift of voltage dependence caused by AaIT (~2-fold).

Intrathecal administration of naringenin improves motor dysfunction and neuropathic pain following compression spinal cord injury in rats: relevance to its antioxidant and anti-inflammatory activities

  • Fakhri, Sajad;Sabouri, Shahryar;Kiani, Amir;Farzaei, Mohammad Hosein;Rashidi, Khodabakhsh;Mohammadi-Farani, Ahmad;Mohammadi-Noori, Ehsan;Abbaszadeh, Fatemeh
    • The Korean Journal of Pain
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    • v.35 no.3
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    • pp.291-302
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    • 2022
  • Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

Central Auditory Processing Tests as Diagnostic Tools for the Early Identification of Elderly Individuals with Mild Cognitive Impairment

  • Jalaei, Bahram;Valadbeigi, Ayub;Panahi, Rasool;Nahrani, Morteza Hamidi;Arefi, Hossein Namvar;Zia, Maryam;Ranjbar, Nastaran
    • Journal of Audiology & Otology
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    • v.23 no.2
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    • pp.83-88
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    • 2019
  • Background and Objectives: Mild cognitive impairment (MCI) is a disorder that usually occurs in the elderly, leading to dementia in some progressive cases. The purpose of this study is to examine the utility of central auditory processing tests as early diagnostic tools for identifying the elderly with MCI. Subjects and Methods: This study was conducted on 20 elderly patients with MCI and 20 healthy matched peers. The speech perception ability in a quiet environment and in the presence of background noise and also temporal resolution were assessed by using Speech Perception in Noise (SPIN) and Gap in Noise (GIN) tests, respectively. Results: The results indicated that the ability to understand speech in a quiet environment did not differ significantly between the two groups. However, SPIN at the three signal-to-noise ratios and the temporal resolution scores were significantly different between the two groups (p<0.001). Conclusions: Individuals with MCI appear to have poorer speech comprehension in noise and a lower temporal resolution than those of the same age, but without cognitive defects. Considering the utility of these tests in identifying cognitive problems, we propose that since the GIN test seems to be less influenced by intervening factors, this test can therefore, be a useful tool for the early screening of elderly people with cognitive problems.