• 대한수의학회지
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• 제52권2호
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• pp.99-104
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• 2012

The present study was performed to evaluate the relationship between the neurotoxicity of acrylamide and the differential gene expression pattern in mice. Both locomotor test and rota-rod test showed that the group treated with higher than 30 mg/kg/day of acrylamide caused impaired motor activity in mice. Based on cDNA microarray analysis of mouse brain, myelin basic protein gene, kinesin family member 5B gene, and fibroblast growth factor (FGF) 1 and its receptor genes were down-regulated by acrylamide. The genes are known to be essential for neurofilament synthesis, axonal transport, and neuroprotection, respectively. Interestingly, both FGF 1 and its receptor genes were down-regulated. Genes involved in nucleic acid binding such as AU RNA binding protein/enoyl-coA hydratase, translation initiation factor (TIF) 2 alpha kinase 4, activating transcription factor 2, and U2AF 1 related sequence 1 genes were down-regulated. More interesting finding was that genes of both catalytic and regulatory subunit of protein phosphatases which are important for signal transduction pathways were down-regulated. Here, we propose that acrylamide induces neurotoxicity by regulation of genes associated with neurofilament synthesis, axonal transport, neuro-protection, and signal transduction pathways.

• The Korean Journal of Physiology
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• 제28권1호
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• pp.99-103
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• 1994

Single neuronal activities were recorded in the cuneate nucleus of awake rats during rest and running behavior. Movement-induced changes in somatic sensory transmission were tested by generating post-stimulus time histograms of these neurons' responses to stimulation through eleetrodes chronically implanted under the skin of the forepaw, during control resting behavior and during two standardized speeds of locomotor movement: slow (1.0 steps/s), fast (2.0 steps/s). The magnitudes of firing during these responses were measured and normalized as percentage increases over background firing. The averaged evoked unit responses were facilitated by $+59.3{\pm}12.5%\;and\;+25.6{\pm}5.4%$ (SEM) as compared with resting behavior, during slow and fast movement respectively. This is to be compared with the movement-induced sensory suppressions observed previously in the ventrobasal thalamus $(-31.0%{\pm}1.9%)$ and in the primary somatosensory cortex $(-71.2%{\pm}3.8%)$ of slowly running rats. These results suggest that afferent somatosensory information may be uniquely modulated at each sensory relay, such that it may be facilitated at brainstem level and then subjected to suppression at higher somatosensory nuclei during movement.

• KSBB Journal
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• 제29권1호
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• pp.67-71
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• 2014

Planaria were recently reported to be a simple and sensitive model to investigate the mechanistic aspect of seizure and to screen potential anticonvulsants. Using planarian model, we analyzed the pharmacological effect of ukgansan (UGS), an oriental herbal medicine containing seven medicinal herbs, on the planarian locomotor velocity (pLMV) and glutamate-induced seizure-like activity (pSLA). To test whether D. japonica is suitable for studying anti-seizure agents, we investigated the effect of glutamate on pLMV and pSLA in D. japonica. In the present study we first confirmed that pSLA in D. japonica was induced by L-glutamate. Glutamate significantly produced pSLA in a dose dependent manner, but did not affect pLMV. These glutamate-induced paroxysms were decreased by antiepileptic drug, topiramate. A similar inhibitory effect on glutamate-induced pSLA was observed after the treatment of UGS. The present results suggest that UGS and its active constituents possess useful substance inhibiting seizure in planarian and that D. japonica provides a convenient model to search active herbs containing anti-seizure activity.

• 한국전문물리치료학회지
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• 제16권2호
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• pp.41-49
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• 2009

This study was designed to investigate the effects of treadmill exercise of low-intensity and moderate- intensity on the functional recovery and histological change in spinal cord injury (SCI) rats. SCI was induced by the spinal cord impactor dropped after laminectomy. Experimental groups were divided into the Group I (normal control), Group II (non-treatment after SCI induction), Group III (low-intensity treadmill exercise after SCI induction), Group IV (moderate-intensity treadmill exercise after SCI induction). After operation, rats were tested at modified Tarlov scale at 2 days with divided into 4 groups, and motor behavior test (BBB locomotor rating scale, Grid walk test) was examined at 3, 7, 14, and 21 days. For the observation of damage change and size of the organized surface in spinal cord, histopathological studies were performed at 21 days by H & E, and BDNF(brain-derived neutrophic factor) & Trk-b immunohistochemistry studies were performed at 1, 3, 7, 14, 21 days. According to the results, treadmill exercise can play a role in facilitating recovery of locomotion following spinal cord injury. Specially, moderate-intensity treadmill exercise after SCI induction was most improvement in functional recovery and histological change.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.904-910
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• 2006

The inhibitory effects of paeonol, a major compound of Paeoniae radix, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated through behavioral experiments. A single administration of morphine produces hyperlocomotion. Repeated administration of morphine develops sensitization (reverse tolerance), a progressive enhancement of locomotion, which is used as a model for studying the drug-induced drug-seeking behaviors, and CPP, which is used as a model for studying drug reinforcement. Paeonol inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, paeonol inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of paeonol. These results provide evidence that paeonol exerts anti-dopaminergic activity, and it is suggested that paeonol may be useful for the prevention and therapy of these adverse actions of morphine.

• Molecules and Cells
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• 제22권3호
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• pp.275-284
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• 2006

The molecular components that generate and maintain circadian rhythms of physiology and behavior in mammals are present both in the brain (suprachiasmatic nucleus; SCN) and in peripheral tissues. Examination of mice with targeted disruptions of either mPer1 or mPer2 has shown that these two genes have key roles in the SCN circadian clock. Here we show that loss of the clock gene mPer2 affects forced locomotor performance in mice without altering muscle contractility. A proteomic analysis revealed that the anterior tibialis muscles of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose phosphate isomerase and enolase than those of either the wild type or mPer1 knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant mice was also significantly higher than in wildtype mice. These results suggest that the reduced locomotor endurance of the mPer2 knockout mice reflects a greater dependence on anaerobic metabolism under stress conditions, and that the two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology of skeletal muscle.

• 동의생리병리학회지
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• 제25권2호
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• pp.257-263
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• 2011

This study was designed to investigate the effects of Hominis placenta pharmacopuncture treatment and electroacupuncture therapy on the functional recovery and histological change, protein expression in spinal cord injury(SCI) rats. Experimental groups were divided into the Group I(normal control rat), Group II(Non-treatment after spinal cord injury induction), Group III(Hominis placenta pharmacopuncture treatment after SCI induction), Group IV (Electroacupuncture therapy after SCI induction), Group V(Hominis placenta pharmacopuncture treatment and electroacupuncture therapy after SCI induction). After operation, rats were tested at modified Tarlov test at 1 to 3 days with divided into 4 groups, and motor behavior test(BBB locomotor rating scale, Grid walk test) was examined at 3, 7, 14, and 21 days. For the observation of damage change and size of the organized surface in muscle and spinal cord, histopathological studies were performed at 21 days by H & E stain, and BDNF & NT-3 protein expression studies were performed at 21 days. Acco rding to the results, Hominis placenta pharmacopuncture treatment and electroacupuncture therapy can play a role in facilitating recovery of locomotion following spinal cord injury. Specially, Hominis placenta pharmacopuncture treatment and electroacupuncture combimed therapy after SCI induction was most improvement in functional recovery, BDNF, and NT-3 protein synthesis.

• Toxicological Research
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• 제20권3호
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• pp.251-261
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• 2004

A large number of chemical pollutants including phthalates, alkylphenolic compounds and organochlorine pesticides have the ability to disrupt endocrine function in animals, and alter cog-nitive function. Because hormone mediated events play an important role in central nervous system development and function, the changes in cognitive function seem to be mediated by the endocrine-like action of these chemicals. The present study therefore was designed to investigate effect of bisphenol A (BPA), an endocrine disrupting chemical on neuro-behavial patterns, and expression of estrogen receptors and tyrosine hydroxylase, a limiting enzyme of dopamine synthesis pathway. BPA was treated orally for 3 weeks into 3 week old mice, and then the neuro-behavial patterns (stereo-type behaviors such as jumping rearing and forepaw tremor, climbing behavior, tail flick, rotarod and locomotor activity), and the expression of estrogen receptors and tyrosine hydroxylase were deter-mined every 3 week for 9 weeks. During the treatment of BPA, the food uptake and body weight increase were not significantly changed. BPA resulted in the increased stereotype behaviors (jump-ing, rearing and forepaw tremor) 6 or 9 weeks after treatment. The time response to tail flick and locomotor activity were decreased by the treatment of BPA, whereas the time for rotarod was increased by the treatment of BPA. The expression of estrogen receptor alpha and beta was increased in the brain and pituitary gland. Maximum expression was found in the brain after 9 week of 100 mg/kg BPA treatment and in the pituitary gland after 6 week of 100 mg/kg BPA treatment. Tyrosine hydroxylase was increased in dose and time dependent manners in the brain but no change was found in the pituitary gland. The present data show that exposure of BPA in the young mice could alter expression of estrogen receptors and dopamine synthesis pathway, thereby modulate neuro-behavial patterns (increase of stereotype behaviors but decrease locomotor activity).

• 한국식품저장유통학회지
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• 제19권5호
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• pp.767-773
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• 2012

괴각 추출물의 항불안 효능을 탐색하기 위하여 elevated plus-maze, horizontal wire test 및 open field test와 같은 동물행동실험을 통하여 비교한 결과 다음과 같은 결론을 얻었다. Elevated plus-maze를 이용한 본 연구에서 괴각 추출물의 100 mg/kg, 200 mg/kg 및 400 mg/kg 투여군에서 대조군에 비하여 open arm에서 머무른 시간의 백분율이 증가하였고, open arm으로의 출입 백분율 또한 증가하였다. Elevated plus-maze를 이용한 길항실험에서는 benzodiazepine 수용체의 antagonist인 flumazenil에 의해 괴각 추출물 400 mg/kg의 항불안 효능이 차단되는 것이 관찰되었다. Locomotor activity 측정에서도 괴각 추출물의 모든 용량에서 총 이동거리의 변화가 없었으며, 또한 horizontal wire test에서도 대조군과 괴각 추출물 투여군 사이에 차이를 나타내지 않았다. 결론적으로, 본 연구의 결과에서 괴각의 메탄올 추출물이 elevated plus-maze test, horizontal wire test 및 open field test를 통하여 locomotor activity 및 근육이완이나 진정 등의 부작용이 없으면서 우수한 항불안 작용을 가지는 천연물이라고 생각되어지며 이러한 작용이 특히 GABA 신경계와 관련이 있음을 시사하고 있다. 향후 괴각의 항불안 작용의 평가를 위하여 다양한 실험모델의 개발이 필요할 것으로 생각되며 또한 이러한 작용에 대한 기전 연구가 포괄적이고 다각적으로 진행되어져야 할 필요성이 있다고 사료된다.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.122-129
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• 2017

A diversity of synthetic cathinones has flooded the recreational drug marketplace worldwide. This variety is often a response to legal control actions for one specific compound (e.g. methcathinone) which has resulted in the emergence of closely related replacement. Based on recent trends, the nitrogen atom is one of the sites in the cathinone molecule being explored by designer type modifications. In this study, we designed and synthesized two new synthetic cathinones, (1) ${\alpha}-piperidinopropiophenone$ (PIPP) and (2) ${\alpha}-piperidinopentiothiophenone$ (PIVT), which have piperidine ring substituent on their nitrogen atom. Thereafter, we evaluated whether these two compounds have an abuse potential through the conditioned place preference (CPP) in mice and self-administration (SA) in rats. We also investigated whether the substances can induce locomotor sensitization in mice following 7 days daily injection and challenge. qRT-PCR analyses were conducted to determine their effects on dopamine-related genes in the striatum. PIPP (10 and 30 mg/kg) induced CPP in mice, but not PIVT. However, both synthetic cathinones were not self-administered by the rats and did not induce locomotor sensitization in mice. qRT-PCR analyses showed that PIPP, but not PIVT, reduced dopamine transporter gene expression in the striatum. These data indicate that PIPP, but not PIVT, has rewarding effects, which may be attributed to its ability to affect dopamine transporter gene expression. Altogether, this study suggests that PIPP may have abuse potential. Careful monitoring of this type of cathinone and related drugs are advocated.