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Volumn 243, Issue 1, 2013, Pages 53-60

Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response

Author keywords

Brain; Catalepsy; Emotional stress; Mice; MRI; Serotonin

Indexed keywords

CORTICOSTERONE; SEROTONIN;

EID: 84872570569     PISSN: 01664328     EISSN: 18727549     Source Type: Journal    
DOI: 10.1016/j.bbr.2012.12.057     Document Type: Article
Times cited : (14)

References (64)
  • 1
    • 17944373029 scopus 로고    scopus 로고
    • Ethological strategies for defence in animals and humans: their role in some psychiatric disorders
    • Dixon A.K. Ethological strategies for defence in animals and humans: their role in some psychiatric disorders. British Journal of Medical Psychology 1998, 71(Pt 4):417-445.
    • (1998) British Journal of Medical Psychology , vol.71 , Issue.PART 4 , pp. 417-445
    • Dixon, A.K.1
  • 5
    • 61649084954 scopus 로고    scopus 로고
    • Catatonia as a risk factor for the development of neuroleptic malignant syndrome: report of a case following treatment with clozapine
    • Paparrigopoulos T., Tzavellas E., Ferentinos P., Mourikis I., Liappas J. Catatonia as a risk factor for the development of neuroleptic malignant syndrome: report of a case following treatment with clozapine. World Journal of Biological Psychiatry 2009, 10:70-73.
    • (2009) World Journal of Biological Psychiatry , vol.10 , pp. 70-73
    • Paparrigopoulos, T.1    Tzavellas, E.2    Ferentinos, P.3    Mourikis, I.4    Liappas, J.5
  • 7
    • 0029763907 scopus 로고    scopus 로고
    • Serotonergic mechanisms in neuroleptic-induced catalepsy in the rat
    • Wadenberg M.L. Serotonergic mechanisms in neuroleptic-induced catalepsy in the rat. Neuroscience and Biobehavioral Reviews 1996, 20:325-339.
    • (1996) Neuroscience and Biobehavioral Reviews , vol.20 , pp. 325-339
    • Wadenberg, M.L.1
  • 10
    • 33750498284 scopus 로고    scopus 로고
    • Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice
    • Kondaurova E.M., Bazovkina D.V., Kulikov A.V., Popova N.K. Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice. Genes, Brain and Behavior 2006, 5:596-601.
    • (2006) Genes, Brain and Behavior , vol.5 , pp. 596-601
    • Kondaurova, E.M.1    Bazovkina, D.V.2    Kulikov, A.V.3    Popova, N.K.4
  • 12
    • 33644696450 scopus 로고    scopus 로고
    • Selection for the predisposition to catalepsy enhances depressive-like traits in mice
    • [in Russian]
    • Bazovkina D.V., Kulikova A.V., Kondaurova E.M., Popova N.K. Selection for the predisposition to catalepsy enhances depressive-like traits in mice. Genetika 2005, 41:1222-1228. [in Russian].
    • (2005) Genetika , vol.41 , pp. 1222-1228
    • Bazovkina, D.V.1    Kulikova, A.V.2    Kondaurova, E.M.3    Popova, N.K.4
  • 13
    • 77954711643 scopus 로고    scopus 로고
    • Effects of chronic fluoxetine treatment on manifestation of sexual motivation and social behavior in mice of ASC line
    • [in Russian]
    • Tikhonova M.A., Otroshchenko E.A., Kulikov A.V. Effects of chronic fluoxetine treatment on manifestation of sexual motivation and social behavior in mice of ASC line. Rossiiskii Fiziologicheskii Zhurnal Imeni I. M. Sechenova 2010, 96:163-172. [in Russian].
    • (2010) Rossiiskii Fiziologicheskii Zhurnal Imeni I. M. Sechenova , vol.96 , pp. 163-172
    • Tikhonova, M.A.1    Otroshchenko, E.A.2    Kulikov, A.V.3
  • 14
    • 67349222846 scopus 로고    scopus 로고
    • Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy
    • Dubrovina N.I., Zinov'ev D.R., Zinov'eva D.V., Kulikov A.V. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy. Neuroscience and Behavioral Physiology 2009, 39:475-480.
    • (2009) Neuroscience and Behavioral Physiology , vol.39 , pp. 475-480
    • Dubrovina, N.I.1    Zinov'ev, D.R.2    Zinov'eva, D.V.3    Kulikov, A.V.4
  • 17
    • 77955541232 scopus 로고    scopus 로고
    • Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes
    • Tikhonova M.A., Alperina E.L., Tolstikova T.G., Bazovkina D.V., Di V.Y., Idova G.V., et al. Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes. Neuroscience and Behavioral Physiology 2010, 40:521-527.
    • (2010) Neuroscience and Behavioral Physiology , vol.40 , pp. 521-527
    • Tikhonova, M.A.1    Alperina, E.L.2    Tolstikova, T.G.3    Bazovkina, D.V.4    Di, V.Y.5    Idova, G.V.6
  • 19
    • 77954425445 scopus 로고    scopus 로고
    • Intracerebral administration of brain-derived neurotrophic factor (BDNF) reduces severity of cataleptic freezing in mice with genetic predisposition to catalepsy
    • Tikhonova M.A., Kulikov A.V., Naumenko V.S., Morozova M.V., Bazovkina D.V., Popova N.K. Intracerebral administration of brain-derived neurotrophic factor (BDNF) reduces severity of cataleptic freezing in mice with genetic predisposition to catalepsy. Bulletin of Experimental Biology and Medicine 2009, 148:889-891.
    • (2009) Bulletin of Experimental Biology and Medicine , vol.148 , pp. 889-891
    • Tikhonova, M.A.1    Kulikov, A.V.2    Naumenko, V.S.3    Morozova, M.V.4    Bazovkina, D.V.5    Popova, N.K.6
  • 20
    • 84861824400 scopus 로고    scopus 로고
    • Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains
    • Naumenko V.S., Kondaurova E.M., Bazovkina D.V., Tsybko A.S., Tikhonova M.A., Kulikov A.V., et al. Effect of brain-derived neurotrophic factor on behavior and key members of the brain serotonin system in genetically predisposed to behavioral disorders mouse strains. Neuroscience 2012, 214:59-67.
    • (2012) Neuroscience , vol.214 , pp. 59-67
    • Naumenko, V.S.1    Kondaurova, E.M.2    Bazovkina, D.V.3    Tsybko, A.S.4    Tikhonova, M.A.5    Kulikov, A.V.6
  • 21
    • 0028997781 scopus 로고
    • On the role of brain serotonin in expression of genetic predisposition to catalepsy in animal models
    • Popova N.K., Kulikov A.V. On the role of brain serotonin in expression of genetic predisposition to catalepsy in animal models. American Journal of Medical Genetics 1995, 60:214-220.
    • (1995) American Journal of Medical Genetics , vol.60 , pp. 214-220
    • Popova, N.K.1    Kulikov, A.V.2
  • 22
    • 67649995436 scopus 로고    scopus 로고
    • Catecholaminergic systems in stress: structural and molecular genetic approaches
    • Kvetnansky R., Sabban E.L., Palkovits M. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiological Reviews 2009, 89:535-606.
    • (2009) Physiological Reviews , vol.89 , pp. 535-606
    • Kvetnansky, R.1    Sabban, E.L.2    Palkovits, M.3
  • 25
    • 19944371237 scopus 로고    scopus 로고
    • Stress, depression, and anhedonia: caveats concerning animal models
    • Anisman H., Matheson K. Stress, depression, and anhedonia: caveats concerning animal models. Neuroscience and Biobehavioral Reviews 2005, 29:525-546.
    • (2005) Neuroscience and Biobehavioral Reviews , vol.29 , pp. 525-546
    • Anisman, H.1    Matheson, K.2
  • 26
    • 77954335850 scopus 로고    scopus 로고
    • Genetic control of catalepsy in mice
    • Nova Science Publishers, NewYork, S.L. Torres, M.S. Marin (Eds.)
    • Kulikov A.V., Popova N.K. Genetic control of catalepsy in mice. Genetic predisposition to disease 2008, 215-236. Nova Science Publishers, NewYork. S.L. Torres, M.S. Marin (Eds.).
    • (2008) Genetic predisposition to disease , pp. 215-236
    • Kulikov, A.V.1    Popova, N.K.2
  • 29
    • 0025983862 scopus 로고
    • One experience with'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability
    • Antelman S.M., Caggiula A.R., Kocan D., Knopf S., Meyer D., Edwards D.J., et al. One experience with'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability. Brain Research 1991, 566:276-283.
    • (1991) Brain Research , vol.566 , pp. 276-283
    • Antelman, S.M.1    Caggiula, A.R.2    Kocan, D.3    Knopf, S.4    Meyer, D.5    Edwards, D.J.6
  • 30
    • 0026596596 scopus 로고
    • Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs
    • Antelman S.M., Caggiula A.R., Knopf S., Kocan D.J., Edwards D.J. Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine; evidence for the stressful/foreign nature of drugs. Psychopharmacology (Berlin) 1992, 107:331-336.
    • (1992) Psychopharmacology (Berlin) , vol.107 , pp. 331-336
    • Antelman, S.M.1    Caggiula, A.R.2    Knopf, S.3    Kocan, D.J.4    Edwards, D.J.5
  • 31
    • 0035076388 scopus 로고    scopus 로고
    • Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI)
    • Kooy R.F., Verhoye M., Lemmon V., Van Der Linden A. Brain studies of mouse models for neurogenetic disorders using in vivo magnetic resonance imaging (MRI). European Journal of Human Genetics 2001, 9:153-159.
    • (2001) European Journal of Human Genetics , vol.9 , pp. 153-159
    • Kooy, R.F.1    Verhoye, M.2    Lemmon, V.3    Van Der Linden, A.4
  • 33
    • 57449088803 scopus 로고    scopus 로고
    • Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease
    • Sawiak S.J., Wood N.I., Williams G.B., Morton A.J., Carpenter T.A. Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease. Neurobiology of Disease 2009, 33:12-19.
    • (2009) Neurobiology of Disease , vol.33 , pp. 12-19
    • Sawiak, S.J.1    Wood, N.I.2    Williams, G.B.3    Morton, A.J.4    Carpenter, T.A.5
  • 34
    • 45849094758 scopus 로고    scopus 로고
    • Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease
    • Lau J.C., Lerch J.P., Sled J.G., Henkelman R.M., Evans A.C., Bedell B.J. Longitudinal neuroanatomical changes determined by deformation-based morphometry in a mouse model of Alzheimer's disease. Neuroimage 2008, 42:19-27.
    • (2008) Neuroimage , vol.42 , pp. 19-27
    • Lau, J.C.1    Lerch, J.P.2    Sled, J.G.3    Henkelman, R.M.4    Evans, A.C.5    Bedell, B.J.6
  • 35
    • 0035200311 scopus 로고    scopus 로고
    • Tracking brain volume changes in C57BL/6J and ApoE-deficient mice in a model of neurodegeneration: a 5-week longitudinal micro-MRI study
    • McDaniel B., Sheng H., Warner D.S., Hedlund L.W., Benveniste H. Tracking brain volume changes in C57BL/6J and ApoE-deficient mice in a model of neurodegeneration: a 5-week longitudinal micro-MRI study. Neuroimage 2001, 14:1244-1255.
    • (2001) Neuroimage , vol.14 , pp. 1244-1255
    • McDaniel, B.1    Sheng, H.2    Warner, D.S.3    Hedlund, L.W.4    Benveniste, H.5
  • 37
    • 54049133277 scopus 로고    scopus 로고
    • The molecular neurobiology of depression
    • Krishnan V., Nestler E.J. The molecular neurobiology of depression. Nature 2008, 455:894-902.
    • (2008) Nature , vol.455 , pp. 894-902
    • Krishnan, V.1    Nestler, E.J.2
  • 38
    • 0034887389 scopus 로고    scopus 로고
    • Stressor specificity of central neuroendocrine responses: implications for stress-related disorders
    • Pacak K., Palkovits M. Stressor specificity of central neuroendocrine responses: implications for stress-related disorders. Endocrine Reviews 2001, 22:502-548.
    • (2001) Endocrine Reviews , vol.22 , pp. 502-548
    • Pacak, K.1    Palkovits, M.2
  • 40
    • 0025372712 scopus 로고
    • The effects of psychological stress on plasma interleukin-6 activity in rats
    • LeMay L.G., Vander A.J., Kluger M.J. The effects of psychological stress on plasma interleukin-6 activity in rats. Physiology and Behavior 1990, 47:957-961.
    • (1990) Physiology and Behavior , vol.47 , pp. 957-961
    • LeMay, L.G.1    Vander, A.J.2    Kluger, M.J.3
  • 41
    • 0342601504 scopus 로고    scopus 로고
    • The influence of restraint stress on the expression of mRNAs for IL-6 and the IL-6 receptor in the hypothalamus and midbrain of the rat
    • [PL]
    • Shizuya K., Komori T., Fujiwara R., Miyahara S., Ohmori M., Nomura J. The influence of restraint stress on the expression of mRNAs for IL-6 and the IL-6 receptor in the hypothalamus and midbrain of the rat. Life Sciences 1997, 61:135-140. [PL].
    • (1997) Life Sciences , vol.61 , pp. 135-140
    • Shizuya, K.1    Komori, T.2    Fujiwara, R.3    Miyahara, S.4    Ohmori, M.5    Nomura, J.6
  • 42
    • 0028505344 scopus 로고
    • Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release
    • Mekaouche M., Givalois L., Barbanel G., Siaud P., Maurel D., Malaval F., et al. Chronic restraint enhances interleukin-1-beta release in the basal state and after an endotoxin challenge, independently of adrenocorticotropin and corticosterone release. Neuroimmunomodulation 1994, 1:292-299.
    • (1994) Neuroimmunomodulation , vol.1 , pp. 292-299
    • Mekaouche, M.1    Givalois, L.2    Barbanel, G.3    Siaud, P.4    Maurel, D.5    Malaval, F.6
  • 44
    • 0032055840 scopus 로고    scopus 로고
    • The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety
    • Maes M., Song C., Lin A., De Jongh R., Van Gastel A., Kenis G., et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 1998, 10:313-318.
    • (1998) Cytokine , vol.10 , pp. 313-318
    • Maes, M.1    Song, C.2    Lin, A.3    De Jongh, R.4    Van Gastel, A.5    Kenis, G.6
  • 45
    • 0028921364 scopus 로고
    • Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat
    • Shintani F., Nakaki T., Kanba S., Sato K., Yagi G., Shiozawa M., et al. Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat. Journal of Neuroscience 1995, 15:1961-1970.
    • (1995) Journal of Neuroscience , vol.15 , pp. 1961-1970
    • Shintani, F.1    Nakaki, T.2    Kanba, S.3    Sato, K.4    Yagi, G.5    Shiozawa, M.6
  • 46
    • 78650226131 scopus 로고    scopus 로고
    • Map3k1, Il6st, Gzmk, and Hspb3 gene coexpression network in the mechanism of freezing reaction in mice
    • Kondaurova E.M., Naumenko V.S., Sinyakova N.A., Kulikov A.V. Map3k1, Il6st, Gzmk, and Hspb3 gene coexpression network in the mechanism of freezing reaction in mice. Journal of Neuroscience Research 2011, 89:267-273.
    • (2011) Journal of Neuroscience Research , vol.89 , pp. 267-273
    • Kondaurova, E.M.1    Naumenko, V.S.2    Sinyakova, N.A.3    Kulikov, A.V.4
  • 47
    • 78650521504 scopus 로고    scopus 로고
    • Effects of lipopolysaccharide and interleukin-6 on cataleptic immobility and locomotor activity in mice
    • Bazovkina D.V., Tibeikina M.A., Kulikov A.V., Popova N.K. Effects of lipopolysaccharide and interleukin-6 on cataleptic immobility and locomotor activity in mice. Neuroscience Letters 2011, 487:302-304.
    • (2011) Neuroscience Letters , vol.487 , pp. 302-304
    • Bazovkina, D.V.1    Tibeikina, M.A.2    Kulikov, A.V.3    Popova, N.K.4
  • 49
    • 0023894017 scopus 로고
    • Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation
    • Pitman D.L., Ottenweller J.E., Natelson B.H. Plasma corticosterone levels during repeated presentation of two intensities of restraint stress: chronic stress and habituation. Physiology and Behavior 1988, 43:47-55.
    • (1988) Physiology and Behavior , vol.43 , pp. 47-55
    • Pitman, D.L.1    Ottenweller, J.E.2    Natelson, B.H.3
  • 50
    • 33845505695 scopus 로고    scopus 로고
    • Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats
    • Marin M.T., Cruz F.C., Planeta C.S. Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats. Physiology and Behavior 2007, 90:29-35.
    • (2007) Physiology and Behavior , vol.90 , pp. 29-35
    • Marin, M.T.1    Cruz, F.C.2    Planeta, C.S.3
  • 52
    • 0023759468 scopus 로고
    • Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (2)
    • Gold P.W., Goodwin F.K., Chrousos G.P. Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (2). New England Journal of Medicine 1988, 319:413-420.
    • (1988) New England Journal of Medicine , vol.319 , pp. 413-420
    • Gold, P.W.1    Goodwin, F.K.2    Chrousos, G.P.3
  • 56
    • 41949091553 scopus 로고    scopus 로고
    • Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus
    • Marais L., van Rensburg S.J., van Zyl J.M., Stein D.J., Daniels W.M. Maternal separation of rat pups increases the risk of developing depressive-like behavior after subsequent chronic stress by altering corticosterone and neurotrophin levels in the hippocampus. Neuroscience Research 2008, 61:106-112.
    • (2008) Neuroscience Research , vol.61 , pp. 106-112
    • Marais, L.1    van Rensburg, S.J.2    van Zyl, J.M.3    Stein, D.J.4    Daniels, W.M.5
  • 57
    • 77953589444 scopus 로고    scopus 로고
    • Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats
    • Brummelte S., Galea L.A. Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats. Neuroscience 2010, 168:680-690.
    • (2010) Neuroscience , vol.168 , pp. 680-690
    • Brummelte, S.1    Galea, L.A.2
  • 58
    • 84856190425 scopus 로고    scopus 로고
    • Stress, stress hormones, and adult neurogenesis
    • Schoenfeld T.J., Gould E. Stress, stress hormones, and adult neurogenesis. Experimental Neurology 2012, 233:12-21.
    • (2012) Experimental Neurology , vol.233 , pp. 12-21
    • Schoenfeld, T.J.1    Gould, E.2
  • 59
    • 77955073943 scopus 로고    scopus 로고
    • Study of the association between catalepsy, anxiety, aggression and depressive-like behavior in congenic mice
    • [in Russian]
    • Kondaurova E.M., Bazovkina D.V., Kulikov A.V. Study of the association between catalepsy, anxiety, aggression and depressive-like behavior in congenic mice. Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova 2010, 96:464-471. [in Russian].
    • (2010) Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova , vol.96 , pp. 464-471
    • Kondaurova, E.M.1    Bazovkina, D.V.2    Kulikov, A.V.3
  • 60
    • 79151479882 scopus 로고    scopus 로고
    • Effect of selective agonist of serotonin 5-HT1A receptors on defensive behavior in mice with different predisposition to catalepsy
    • Bazovkina D.V., Terenina E.E., Kulikov A.V. Effect of selective agonist of serotonin 5-HT1A receptors on defensive behavior in mice with different predisposition to catalepsy. Bulletin of Experimental Biology and Medicine 2010, 150:225-228.
    • (2010) Bulletin of Experimental Biology and Medicine , vol.150 , pp. 225-228
    • Bazovkina, D.V.1    Terenina, E.E.2    Kulikov, A.V.3
  • 61
    • 84862683721 scopus 로고    scopus 로고
    • A new synthetic varacin analogue, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), decreased hereditary catalepsy and increased the BDNF gene expression in the hippocampus in mice
    • Kulikov A.V., Tikhonova M.A., Kulikova E.A., Volcho K.P., Khomenko T.M., Salakhutdinov N.F., et al. A new synthetic varacin analogue, 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), decreased hereditary catalepsy and increased the BDNF gene expression in the hippocampus in mice. Psychopharmacology (Berlin) 2012, 221:469-478.
    • (2012) Psychopharmacology (Berlin) , vol.221 , pp. 469-478
    • Kulikov, A.V.1    Tikhonova, M.A.2    Kulikova, E.A.3    Volcho, K.P.4    Khomenko, T.M.5    Salakhutdinov, N.F.6
  • 63
  • 64
    • 37849040422 scopus 로고    scopus 로고
    • Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons
    • Sano K., Mishima K., Koushi E., Orito K., Egashira N., Irie K., et al. Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons. Neuroscience 2008, 151:320-328.
    • (2008) Neuroscience , vol.151 , pp. 320-328
    • Sano, K.1    Mishima, K.2    Koushi, E.3    Orito, K.4    Egashira, N.5    Irie, K.6


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.