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GRIN3A가 과발현된 유전자 조작 마우스의 행동특성 연구
우태선,정재훈,Woo, Taeseon,Cheong, Jae Hoon 대한약학회 2016 약학회지 Vol.60 No.4
N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play a significant role in synaptic plasticity, learning, memory, and other behaviors. NMDARs are composed of various subunits and display unique properties depending on their subunit composition. The GluN3A subunit is thought to suppress NMDAR activity, however its exact function has not been well studied. Thus, we designed a transgenic mice overexpressing GRIN3A to assess the role of this gene on various behaviors. GRIN3A-overexpressing mice were subjected to an array of behavioral experiments including locomotor activity test, rota-rod test, elevated plus-maze (EPM) test, and Y-maze test. GRIN3A-overexpressing mice displayed hypoactivity but no effects on the rota-rod test, EPM test and Y-maze test. The GRIN3A-overexpressing mice that we have created can be utilized in elucidating the role of the GRIN3A gene and its product, the GluN3A subunit of NMDARs, on various behaviors associated with neuropsychiatric disorders, such as ADHD, and in finding possible therapeutic targets for these disorders.
최윤정(Yun Jung Choi),윤서영(Seo Young Yoon),최지영(Ji Young Choi),우태선(Tae Seon Woo),손건호(Kun Ho Son),이용수(Yong Soo Lee),정재훈(Jae Hoon Cheong) 대한약학회 2011 약학회지 Vol.55 No.3
The aim of this study is to evaluate the sedative effects of ethanol extract and the three major constituents of Cimicifugae Rhizoma. They decreased locomotor activity significantly, and enhanced sleeping duration induced by thiopental sodium. The ethanol extract of Cimicifugae rhizoma and 24-epi-7,8-didehydrocimigenol-3-xyloside (24-epi.) increased the Cl- influx into the intracellular area of SH-SY5Y neuroblastoma cells significantly. The present results demonstrate that the sedative effects of Cimicifugae rhizoma are mediated via the GABA-gated Cl- channel, partly by 24-epi.
Raly James Perez Custodio,Chrislean Jun Botanas,윤성순,June Bryan de la Peña,Irene Joy dela Peña,김미경,우태선,서정욱,장춘곤,권용호,김남용,이용섭,김희진,정재훈 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.6
Recently, there has been a rise in the number of amphetamine derivatives that serve as substitutes for controlled substances (e.g. amphetamine and methamphetamine) on the global illegal drug market. These substances are capable of producing rewarding effects similar to their parent drug. In anticipation of the future rise of new and similar psychoactive substances, we designed and synthesized four novel amphetamine derivatives with N-benzyl, N-benzylamphetamine HCl (NBNA) substituent on the amine region, 1,4-dioxane ring, ethylenedioxy-amphetamine HCl (EDA), methyl, para-methylamphetamine HCl (PMEA), and naphthalene, 2-(aminopropyl) naphthalene HCl (2-APN) substituents on the phenyl site. Then, we evaluated their abuse potential in the conditioned place preference (CPP) test in mice and self-administration (SA) test in rats. We also investigated the psychostimulant properties of the novel drugs using the locomotor sensitization test in mice. Moreover, we performed qRT-PCR analyses to explore the effects of the novel drugs on the expression of D1 and D2 dopamine receptor genes in the striatum. NBNA, but not EDA, PMEA, and 2-APN, induced CPP and SA in rodents. None of the test drugs have produced locomotor sensitization. qRT-PCR analyses demonstrated that NBNA increased the expression of striatal D1 dopamine receptor genes. These data indicate that NBNA yields rewarding effects, suggesting potential for abuse. Continual observation for the rise of related substances is thus strongly encouraged.
김미경,김희진,김성목,June Bryan de la Peña,Irene Joy dela Peña,Chrislean Jun Botanas,우태선,이용수,류종훈,정재훈 한국생약학회 2017 Natural Product Sciences Vol.23 No.1
Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on Cl- influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular Cl- influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.