{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:58:05Z","timestamp":1787025485897,"version":"build-2736575974"},"reference-count":80,"publisher":"IMR Press","issue":"2","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>We evaluated the practicability of using the rarely utilized C57BL\/6N mouse as a Parkinson\u2019s disease model established via the acute MPTP\/probenecid (MPTP\/p) protocol. We confirmed dopaminergic degeneration in terms of decreased expression levels of tyrosine hydroxylase in the substantia nigra and striatum of MPTP\/p-lesioned mice. In addition, acute MPTP\/p-lesioned mice demonstrated initial motor dysfunctions followed by spontaneous recovery. Interestingly, these MPTP\/p-lesioned mice exhibited anxiolytic and antidepressive behaviors upon recovery from these motor deficits. Additionally, increased expression of norepinephrine transporters in several brain regions, including the hippocampus, medial prefrontal cortex, and striatum, and an elevated rate of adult neurogenesis (in terms of increased numbers of doublecortin-positive neuroblasts) in the hippocampus were observed after recovery from motor dysfunctions. We suggest that the emotional alterations observed under these experimental conditions may be associated with enhanced adult neurogenesis, increased levels of norepinephrine transporters, and\/or a possible interplay between these two factors. Consequently, this acute MPTP\/p model adequately satisfies the criteria for the validity of a Parkinson\u2019s disease model regarding dopaminergic loss and motor impairment. However, the non-motor findings may offer novel evidence against the practicability of utilizing the acute MPTP\/p-lesioned mice for modeling the emotional aberrations found in Parkinson\u2019s disease patients.<\/jats:p>","DOI":"10.31083\/j.jin2002030","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T01:04:01Z","timestamp":1625447041000},"source":"Crossref","is-referenced-by-count":22,"title":["Behavioral characterization in MPTP\/p mouse model of Parkinson\u2019s disease"],"prefix":"10.31083","volume":"20","author":[{"given":"Mai","family":"Wada","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jasmin","family":"Ang","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poornima D. E.","family":"Weerasinghe-Mudiyanselage","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Ho","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Choon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekyun","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, 63243 Jeju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjong","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Rojas NG, Cesarini M, Etcheverry JL, Prat GAD, Arciuch VA, Gatto EM. Neurodegenerative diseases and cancer: sharing common mechanisms in complex interactions. Journal of Integrative Neuroscience. 2020; 19: 187\u2013199.","DOI":"10.31083\/j.jin.2020.01.3"},{"key":"ref2","unstructured":"Przedborski S, Jackson-Lewis V. Mechanisms of MPTP toxicity. Movement Disorders 1998; 13: 35\u201338."},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Langston JW, Irwin I. MPTP: current concepts and controversies. Clinical Neuropharmacology. 1986; 9: 485\u2013507.","DOI":"10.1097\/00002826-198612000-00001"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Sedelis M, Schwarting RK, Huston JP. Behavioral phenotyping of the MPTP mouse model of Parkinson\u2019s disease. Behavoural Brain Research. 2001; 125: 109\u2013125.","DOI":"10.1016\/S0166-4328(01)00309-6"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Sai T, Uchida K, Nakayama H. Biochemical evaluation of the neurotoxicity of MPTP and MPP+ in embryonic and newborn mice. The Journal of Toxicological Sciences. 2013; 38: 445\u2013458.","DOI":"10.2131\/jts.38.445"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Meredith GE, Rademacher DJ. MPTP mouse models of Parkinson\u2019s disease: an update. Journal of Parkinson\u2019s Disease. 2011; 1: 19\u201333.","DOI":"10.3233\/JPD-2011-11023"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Luchtman DW, Shao D, Song C. Behavior, neurotransmitters and inflammation in three regimens of the MPTP mouse model of Parkinson\u2019s disease. Physiology & Behavior. 2009; 98: 130\u2013138.","DOI":"10.1016\/j.physbeh.2009.04.021"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Pain S, Gochard A, Bodard S, Gulhan Z, Prunier-Aesch C, Chalon S. Toxicity of MPTP on neurotransmission in three mouse models of Parkinson\u2019s disease. Experimental and Toxicologic Pathology. 2013; 65: 689\u2013694.","DOI":"10.1016\/j.etp.2012.09.001"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Emborg ME. Evaluation of animal models of Parkinson\u2019s disease for neuroprotective strategies. Journal of Neuroscience Methods. 2004; 139: 121\u2013143.","DOI":"10.1016\/j.jneumeth.2004.08.004"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Gorton LM, Vuckovic MG, Vertelkina N, Petzinger GM, Jakowec MW, Wood RI. Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse. Behavioural Brain Research. 2010; 213: 253\u2013262.","DOI":"10.1016\/j.bbr.2010.05.009"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Sampaio TB, Sari MHM, Pesarico AP, Mantovani AC, Zeni G, Nogueira CW. 7-Fluoro-1,3-diphenylisoquinoline reverses motor and non-motor symptoms induced by MPTP in mice: role of striatal neuroinflammation. European Journal of Pharmacology. 2018; 819: 129\u2013135.","DOI":"10.1016\/j.ejphar.2017.12.001"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Kim B-W, Koppula S, Kumar H, Park J-Y, Kim I-W, More SV, et al. \u03b1-Asarone attenuates microglia-mediated neuroinflammation by inhibiting NF kappa B activation and mitigates MPTP-induced behavioral deficits in a mouse model of Parkinson\u2019s disease. Neuropharmacology. 2015; 97: 46\u201357.","DOI":"10.1016\/j.neuropharm.2015.04.037"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Park J, Lim C-S, Seo H, Park C-A, Zhuo M, Kaang B-K, et al. Pain perception in acute model mice of Parkinson\u2019s disease induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Molecular Pain. 2015; 11: s12990-12015-10026-12991.","DOI":"10.1186\/s12990-015-0026-1"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Fifel K, Dkhissi-Benyahya O, Cooper HM. Lack of long-term changes in circadian, locomotor, and cognitive functions in acute and chronic MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) mouse models of Parkinson\u2019s disease. Chronobiology International. 2013; 30: 741\u2013755.","DOI":"10.3109\/07420528.2012.762011"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Schildknecht S, Di Monte DA, Pape R, Tieu K, Leist M. Tipping points and endogenous determinants of nigrostriatal degeneration by MPTP. Trends in Pharmacological Sciences. 2017; 38: 541\u2013555.","DOI":"10.1016\/j.tips.2017.03.010"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Lau Y-S, Crampton JM, Wilson JA. Urinary excretion of MPTP and its primary metabolites in mice. Life Sciences. 1988; 43: 1459\u20131464.","DOI":"10.1016\/0024-3205(88)90257-3"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Johannessen JN, Chiueh CC, Burns RS, Markey SP. Differences in the metabolism of MPTP in the rodent and primate parallel differences in sensitivity to its neurotoxic effects. Life Sciences. 1985; 36: 219\u2013224.","DOI":"10.1016\/0024-3205(85)90062-1"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Lau Y-S, Trobough KL, Crampton JM, Wilson JA. Effects of probenecid on striatal dopamine depletion in acute and long-term 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mice. General Pharmacology. 1990; 21: 181\u2013187.","DOI":"10.1016\/0306-3623(90)90898-V"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Petroske E, Meredith G, Callen S, Totterdell S, Lau Y-S. Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP\/probenecid treatment. Neuroscience. 2001; 106: 589\u2013601.","DOI":"10.1016\/S0306-4522(01)00295-0"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Alvarez\u2010Fischer D, Noelker C, Gr\u00fcnewald A, Vulinovi\u0107 F, Guerreiro S, Fuchs J, et al. Probenecid potentiates MPTP\/MPP+ toxicity by interference with cellular energy metabolism. Journal of Neurochemistry. 2013; 127: 782\u2013792.","DOI":"10.1111\/jnc.12343"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Marmiroli P, Riva B, Pozzi E, Ballarini E, Lim D, Chiorazzi A, et al. Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: phenotypic and genotypic insights. PLoS ONE. 2017; 12: e0186250.","DOI":"10.1371\/journal.pone.0186250"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Paigen B, Morrow A, Brandon C, Mitchell D, Holmes P. Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis. 1985; 57: 65\u201373.","DOI":"10.1016\/0021-9150(85)90138-8"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Rogers DC, Fisher E, Brown S, Peters J, Hunter A, Martin J. Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment. Mammalian Genome. 1997; 8: 711\u2013713.","DOI":"10.1007\/s003359900551"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, et al. Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology. 1997; 132: 107\u2013124.","DOI":"10.1007\/s002130050327"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Nadler JJ, Zou F, Huang H, Moy SS, Lauder J, Crawley JN, et al. Large-scale gene expression differences across brain regions and inbred strains correlate with a behavioral phenotype. Genetics. 2006; 174: 1229\u20131236.","DOI":"10.1534\/genetics.106.061481"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Sedelis M, Hofele K, Auburger GW, Morgan S, Huston JP, Schwarting RK. MPTP susceptibility in the mouse: behavioral, neurochemical, and histological analysis of gender and strain differences. Behavior Genetics. 2000; 30: 171\u2013182.","DOI":"10.1023\/A:1001958023096"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Kawashita E, Ishihara K, Nomoto M, Taniguchi M, Akiba S. A comparative analysis of hepatic pathological phenotypes in C57BL\/6J and C57BL\/6N mouse strains in non-alcoholic steatohepatitis models. Scientific Reports. 2019; 9: 204.","DOI":"10.1038\/s41598-018-36862-7"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Simon MM, Greenaway S, White JK, Fuchs H, Gailus-Durner V, Wells S, et al. A comparative phenotypic and genomic analysis of C57BL\/6J and C57BL\/6N mouse strains. Genome Biology. 2013; 14: R82.","DOI":"10.1186\/gb-2013-14-7-r82"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Wang L, Zhai YQ, Xu LL, Qiao C, Sun XL, Ding JH, et al. Metabolic inflammation exacerbates dopaminergic neuronal degeneration in response to acute MPTP challenge in type 2 diabetes mice. Experimental Neurology. 2014; 251: 22\u201329.","DOI":"10.1016\/j.expneurol.2013.11.001"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Thadathil N, Xiao J, Hori R, Alway SE, Khan MM. Brain selective estrogen treatment protects dopaminergic neurons and preserves behavioral function in MPTP-induced mouse model of Parkinson\u2019s disease. Journal of Neuroimmune Pharmacology. 2020. (in press)","DOI":"10.1007\/s11481-020-09972-1"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Farf\u00e1n-Garc\u00eda ED, Abad-Garc\u00eda A, Alatorre A, P\u00e9rez-Capistran T, Querejeta E, Soriano-Urs\u00faa MA. Olive oil limited motor disruption and neuronal damage in parkinsonism induced by MPTP administration. Toxicology Research and Application. 2020; 4: 2397847320922939.","DOI":"10.1177\/2397847320922939"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Ang MJ, Kim J, Lee S, Kim SH, Kim JC, Jeon TI, et al. Transcriptome profiling reveals novel candidate genes related to hippocampal dysfunction in SREBP-1c knockout mice. International Journal of Molecular Sciences. 2020; 21: 4131.","DOI":"10.3390\/ijms21114131"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Ang MJ, Kang S, Moon C. Melatonin alters neuronal architecture and increases cysteine-rich protein 1 signaling in the male mouse hippocampus. Journal of Neuroscience Research. 2020; 98: 2333\u20132348.","DOI":"10.1002\/jnr.24708"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Kang S, Lee S, Kim J, Kim JC, Kim SH, Son Y, et al. Chronic treatment with combined chemotherapeutic agents affects hippocampal micromorphometry and function in mice, independently of neuroinflammation. Experimental Neurobiology. 2018; 27: 419\u2013436.","DOI":"10.5607\/en.2018.27.5.419"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Yang M, Kim J-S, Song M-S, Kim S-H, Kang SS, Bae C-S, et al. Cyclophosphamide impairs hippocampus-dependent learning and memory in adult mice: possible involvement of hippocampal neurogenesis in chemotherapy-induced memory deficits. Neurobiology of Learning and Memory. 2010; 93: 487\u2013494.","DOI":"10.1016\/j.nlm.2010.01.006"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Son Y, Yang M, Kang S, Lee S, Kim J, Kim J, et al. Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus. Neurobiology of Learning and Memory. 2015; 121: 12\u201319.","DOI":"10.1016\/j.nlm.2015.03.002"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Carroll JB, Southwell AL, Graham RK, Lerch JP, Ehrnhoefer DE, Cao L-P, et al. Mice lacking caspase-2 are protected from behavioral changes, but not pathology, in the YAC128 model of Huntington disease. Molecular Neurodegeneration. 2011; 6: 59.","DOI":"10.1186\/1750-1326-6-59"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Kim ST, Son HJ, Choi JH, Ji IJ, Hwang O. Vertical grid test and modified horizontal grid test are sensitive methods for evaluating motor dysfunctions in the MPTP mouse model of Parkinson\u2019s disease. Brain Research. 2010; 1306: 176\u2013183.","DOI":"10.1016\/j.brainres.2009.09.103"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Pellow S, Chopin P, File SE, Briley M. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of Neuroscience Methods. 1985; 14: 149\u2013167.","DOI":"10.1016\/0165-0270(85)90031-7"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Angoa-Perez M, Kane MJ, Briggs DI, Francescutti DM, Kuhn DM. Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. Journal of Visualized Experiments. 2013; 82: e50978.","DOI":"10.3791\/50978-v"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985; 85: 367\u2013370.","DOI":"10.1007\/BF00428203"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Platonova NA, Barabanova SA, Povalikhin RG, Tsymbalenko NV, Nozdrachev AD, Puchkova LV. Expression of Menkes ATPase and Wilson ATPase in different regions of the adult rat brain. Doklady Biological Sciences. 2005; 401: 88\u201391.","DOI":"10.1007\/s10630-005-0052-7"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Meredith GE, Totterdell S, Potashkin JA, Surmeier DJ. Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol. Parkinsonism & Related Disorders. 2008; 14: S112\u2013S115.","DOI":"10.1016\/j.parkreldis.2008.04.012"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Kurosaki R, Muramatsu Y, Kato H, Araki T. Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson\u2019s disease. Pharmacology Biochemistry and Behavior. 2004; 78: 143\u2013153.","DOI":"10.1016\/j.pbb.2004.03.006"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Yang X, Cheng B. Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. Journal of Molecular Neuroscience. 2010; 42: 145\u2013153.","DOI":"10.1007\/s12031-010-9336-y"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Hofele K, Sedelis M, Auburger GW, Morgan S, Huston JP, Schwarting RKW. Evidence for a dissociation between MPTP toxicity and tyrosinase activity based on congenic mouse strain susceptibility. Experimental Neurology. 2001; 168: 116\u2013122.","DOI":"10.1006\/exnr.2000.7588"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Sedelis M, Hofele K, Auburger GW, Morgan S, Huston JP, Schwarting RK. Evidence for resistance to MPTP in C57BL\/6\u00d7 BALA\/c F1 hybrids as compared with their progenitor strains. Neuroreport. 2000; 11: 1093\u20131096.","DOI":"10.1097\/00001756-200004070-00037"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Magrinelli F, Picelli A, Tocco P, Federico A, Roncari L, Smania N, et al. Pathophysiology of motor dysfunction in Parkinson\u2019s disease as the rationale for drug treatment and rehabilitation. Parkinson\u2019s Disease. 2016; 2016: 9832839.","DOI":"10.1155\/2016\/9832839"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"Rousselet E, Joubert C, Callebert J, Parain K, Tremblay L, Orieux G, et al. Behavioral changes are not directly related to striatal monoamine levels, number of nigral neurons, or dose of parkinsonian toxin MPTP in mice. Neurobiology of Disease. 2003; 14: 218\u2013228.","DOI":"10.1016\/S0969-9961(03)00108-6"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Mitsumoto Y, Watanabe A, Mori A, Koga N. Spontaneous regeneration of nigrostriatal dopaminergic neurons in MPTP-treated C57BL\/6 mice. Biochemical and Biophysical Research Communications. 1998; 248: 660\u2013663.","DOI":"10.1006\/bbrc.1998.8986"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Arai A, Tomiyama M, Kannari K, Kimura T, Suzuki C, Watanabe M, et al. Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson\u2019s disease via norepinephrine transporter. Synapse. 2008; 62: 632\u2013635.","DOI":"10.1002\/syn.20535"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Lindgren HS, Dunnett SB. Cognitive dysfunction and depression in Parkinson\u2019s disease: what can be learned from rodent models? European Journal of Neuroscience. 2012; 35: 1894\u20131907.","DOI":"10.1111\/j.1460-9568.2012.08162.x"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Shin KS, Zhao TT, Choi HS, Hwang BY, Lee CK, Lee MK. Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of Parkinson\u2019s disease. Brain Research. 2014; 1567: 57\u201365.","DOI":"10.1016\/j.brainres.2014.04.015"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Dogru NO, Bal R. Effects of Voluntary and forced exercise on anxiety-related behaviours and motor activity in Parkinson mouse model. European Journal of Therapeutics. 2019; 25: 97\u2013104.","DOI":"10.5152\/EurJTher.2018.18011"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Almansoub HA, Tang H, Wu Y, Wang D-Q, Mahaman YAR, Salissou MTM, et al. Oxytocin alleviates MPTP-induced neurotoxicity in mice by targeting microRNA-26a\/death-associated protein kinase 1 pathway. Journal of Alzheimer\u2019s Disease. 2020; 74: 883\u2013901.","DOI":"10.3233\/JAD-191091"},{"key":"ref56","unstructured":"Aruna K, Rajeswari PDR, Sankar SR. The effect of Oxalis corniculata extract against the behavioral changes induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in mice. Journal of Applied Pharmaceutical Science. 2017; 7: 148\u2013153."},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Campolo M, Paterniti I, Siracusa R, Filippone A, Esposito E, Cuzzocrea S. TLR4 absence reduces neuroinflammation and inflammasome activation in Parkinson\u2019s diseases in vivo model. Brain, Behavior, and Immunity. 2019; 76: 236\u2013247.","DOI":"10.1016\/j.bbi.2018.12.003"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Menza MA, Robertson-Hoffman DE, Bonapace AS. Parkinson\u2019s disease and anxiety: comorbidity with depression. Biological Psychiatry. 1993; 34: 465\u2013470.","DOI":"10.1016\/0006-3223(93)90237-8"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Gallagher DA, Schrag A. Psychosis, apathy, depression and anxiety in Parkinson\u2019s disease. Neurobiology of Disease. 2012; 46: 581\u2013589.","DOI":"10.1016\/j.nbd.2011.12.041"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"Zhang T, Hong J, Di T, Chen L. MPTP impairs dopamine D1 receptor-mediated survival of newborn neurons in ventral hippocampus to cause depressive-like behaviors in adult mice. Frontiers in Molecular Neuroscience. 2016; 9: 101.","DOI":"10.3389\/fnmol.2016.00101"},{"key":"ref61","doi-asserted-by":"crossref","unstructured":"Li Y, Jiao Q, Du X, Bi M, Han S, Jiao L, et al. Investigation of behavioral dysfunctions induced by monoamine depletions in a mouse model of Parkinson\u2019s disease. Frontiers in Cellular Neuroscience. 2018; 12: 241.","DOI":"10.3389\/fncel.2018.00241"},{"key":"ref62","doi-asserted-by":"crossref","unstructured":"Mori A, Ohashi S, Nakai M, Moriizumi T, Mitsumoto Y. Neural mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL\/6 mice. Neuroscience Research. 2005; 51: 265\u2013274.","DOI":"10.1016\/j.neures.2004.11.008"},{"key":"ref63","doi-asserted-by":"crossref","unstructured":"Kida K, Yamada M, Tokuda K, Marutani E, Kakinohana M, Kaneki M, et al. Inhaled hydrogen sulfide prevents neurodegeneration and movement disorder in a mouse model of Parkinson\u2019s disease. Antioxidants & Redox Signaling. 2011; 15: 343\u2013352.","DOI":"10.1089\/ars.2010.3671"},{"key":"ref64","doi-asserted-by":"crossref","unstructured":"Li X-M, Ma H-B, Ma Z-Q, Li L-F, Xu C-L, Qu R, et al. Ameliorative and neuroprotective effect in MPTP model of Parkinson\u2019s disease by Zhen-Wu-Tang (ZWT), a traditional Chinese medicine. Journal of Ethnopharmacology. 2010; 130: 19\u201327.","DOI":"10.1016\/j.jep.2010.03.020"},{"key":"ref65","doi-asserted-by":"crossref","unstructured":"Selvakumar GP, Janakiraman U, Essa MM, Thenmozhi AJ, Manivasagam T. Escin attenuates behavioral impairments, oxidative stress and inflammation in a chronic MPTP\/probenecid mouse model of Parkinson\u2019s disease. Brain Research. 2014; 1585: 23\u201336.","DOI":"10.1016\/j.brainres.2014.03.010"},{"key":"ref66","doi-asserted-by":"crossref","unstructured":"Vazey E, Aston-Jones G. The emerging role of norepinephrine in cognitive dysfunctions of Parkinson\u2019s disease. Frontiers in Behavioral Neuroscience. 2012; 6: 48.","DOI":"10.3389\/fnbeh.2012.00048"},{"key":"ref67","doi-asserted-by":"crossref","unstructured":"Remy P, Doder M, Lees A, Turjanski N, Brooks D. Depression in Parkinson\u2019s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain. 2005; 128: 1314\u20131322.","DOI":"10.1093\/brain\/awh445"},{"key":"ref68","doi-asserted-by":"crossref","unstructured":"Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW, et al. Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nature Neuroscience. 2000; 3: 465\u2013471.","DOI":"10.1038\/74839"},{"key":"ref69","doi-asserted-by":"crossref","unstructured":"Zhou J. Norepinephrine transporter inhibitors and their therapeutic potential. Drugs of the Future. 2004; 29: 1235.","DOI":"10.1358\/dof.2004.029.12.855246"},{"key":"ref70","doi-asserted-by":"crossref","unstructured":"Erro R, Pappat\u00e0 S, Amboni M, Vicidomini C, Longo K, Santangelo G, et al. Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson\u2019s disease patients. Parkinsonism & Related Disorders. 2012; 18: 1034\u20131038.","DOI":"10.1016\/j.parkreldis.2012.05.022"},{"key":"ref71","doi-asserted-by":"crossref","unstructured":"Dunlop BW, Nemeroff CB. The role of dopamine in the pathophysiology of depression. Archives of General Psychiatry. 2007; 64: 327\u2013337.","DOI":"10.1001\/archpsyc.64.3.327"},{"key":"ref72","doi-asserted-by":"crossref","unstructured":"Peng J, Xie L, Jin K, Greenberg DA, Andersen JK. Fibroblast growth factor 2 enhances striatal and nigral neurogenesis in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson\u2019s disease. Neuroscience. 2008; 153: 664\u2013670.","DOI":"10.1016\/j.neuroscience.2008.02.063"},{"key":"ref73","doi-asserted-by":"crossref","unstructured":"Peng J, Andersen JK. Mutant \u03b1-synuclein and aging reduce neurogenesis in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson\u2019s disease. Aging Cell. 2011; 10: 255\u2013262.","DOI":"10.1111\/j.1474-9726.2010.00656.x"},{"key":"ref74","doi-asserted-by":"crossref","unstructured":"Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003; 301: 805\u2013809.","DOI":"10.1126\/science.1083328"},{"key":"ref75","doi-asserted-by":"crossref","unstructured":"Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. Journal of Clinical Investigation. 2005; 115: 3104\u20133116.","DOI":"10.1172\/JCI25509"},{"key":"ref76","doi-asserted-by":"crossref","unstructured":"Quesseveur G, David DJ, Gaillard MC, Pla P, Wu MV, Nguyen HT, et al. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities. Transitional Psychiatry. 2013; 3: e253.","DOI":"10.1038\/tp.2013.30"},{"key":"ref77","doi-asserted-by":"crossref","unstructured":"Mishra A, Singh S, Tiwari V, Shukla S. Dopamine D1 receptor activation improves adult hippocampal neurogenesis and exerts anxiolytic and antidepressant-like effect via activation of Wnt\/\u03b2-catenin pathways in rat model of Parkinson\u2019s disease. Neurochemistry International. 2019; 122: 170\u2013186.","DOI":"10.1016\/j.neuint.2018.11.020"},{"key":"ref78","unstructured":"Malberg JE. Implications of adult hippocampal neurogenesis in antidepressant action. Journal of Psychiatry & Neuroscience. 2004; 29: 196\u2013205."},{"key":"ref79","doi-asserted-by":"crossref","unstructured":"Gordon JA, Hen R. The serotonergic system and anxiety. Neuromolecular Medicine. 2004; 5: 27\u201340.","DOI":"10.1385\/NMM:5:1:027"},{"key":"ref80","doi-asserted-by":"crossref","unstructured":"Nakagawa S, Kim JE, Lee R, Malberg JE, Chen J, Steffen C, et al. Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein. Journal of Neuroscience. 2002; 22: 3673\u20133682.","DOI":"10.1523\/JNEUROSCI.22-09-03673.2002"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/20\/2\/10.31083\/j.jin2002030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T10:19:54Z","timestamp":1732702794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/20\/2\/10.31083\/j.jin2002030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":80,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021]]}},"alternative-id":["1625014728953-1784839714"],"URL":"https:\/\/doi.org\/10.31083\/j.jin2002030","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,30]]},"article-number":"307"}}