{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:00:24Z","timestamp":1782399624242,"version":"3.54.5"},"reference-count":73,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T00:00:00Z","timestamp":1354060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2013,3]]},"abstract":"Erythropoietin (Epo) is neuroprotective in a number of preparations, but can lead to unacceptably high and even lethal hematocrit levels. Recent reports show that modified Epo variants confer neuroprotection in models of glaucoma and retinal degeneration without raising hematocrit. In this study, neuroprotective effects of two Epo variants (EpoR76E<\/jats:styled-content> and EpoS71E<\/jats:styled-content>) were assessed in a model of Parkinson's disease. The constructs were packaged in recombinant adeno\u2010associated viral (rAAV<\/jats:styled-content>) vectors and injected intramuscularly. After 3\u2009weeks, mice received five daily injections of 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP<\/jats:styled-content>) and were killed 5\u2009weeks later. The MPTP<\/jats:styled-content>\u2010lesioned mice pretreated with rAAV<\/jats:styled-content>.eGFP<\/jats:styled-content> (negative control) exhibited a 7\u2010 to 9\u2010Hz tremor and slower latencies to move on a grid test (akinesia). Both of these symptomatic features were absent in mice pretreated with either modified Epo construct. The rAAV<\/jats:styled-content>.eGFP<\/jats:styled-content>\u2010treated mice lesioned with MPTP<\/jats:styled-content> exhibited a 41% reduction in tyrosine hydroxylase (TH<\/jats:styled-content>)\u2010positive neurons in the substantia nigra. The rAAV<\/jats:styled-content>.EpoS71E<\/jats:styled-content> construct did not protect nigral neurons, but neuronal loss in mice pretreated with rAAV<\/jats:styled-content>.EpoR76E<\/jats:styled-content> was only half that of rAAV<\/jats:styled-content>.eGFP<\/jats:styled-content> controls. Although dopamine levels were normal in all groups, 3,4\u2010dihydroxyphenylacetic acid (DOPAC) was significantly reduced only in MPTP<\/jats:styled-content>\u2010lesioned mice pretreated with rAAV<\/jats:styled-content>.eGFP<\/jats:styled-content>, indicating reduced dopamine turnover. Analysis of TH<\/jats:styled-content>\u2010positive fibers in the striatum showed normalized density in MPTP<\/jats:styled-content>\u2010lesioned mice pretreated with rAAV<\/jats:styled-content>.EpoS71E<\/jats:styled-content>, suggesting that enhanced sprouting induced by EpoS71E<\/jats:styled-content> may have been responsible for normal behavior and dopaminergic tone in these mice. These results show that systemically administered rAAV<\/jats:styled-content>\u2010generated non\u2010erythropoietic Epo may protect against MPTP<\/jats:styled-content>\u2010induced parkinsonism by a combination of neuroprotection and enhanced axonal sprouting.<\/jats:bold><\/jats:p>","DOI":"10.1111\/gbb.12001","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T01:12:24Z","timestamp":1354151544000},"page":"224-233","source":"Crossref","is-referenced-by-count":25,"title":["A single intramuscular injection of rAAV<\/scp>\u2010mediated mutant erythropoietin protects against MPTP<\/scp>\u2010induced parkinsonism"],"prefix":"10.1111","volume":"12","author":[{"given":"A.","family":"Dhanushkodi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. O.","family":"Akano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. E.","family":"Roguski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. K.","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. G.","family":"Matta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. S.","family":"Rex","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Tennessee Health Science Center Memphis TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. P.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199906000-00007"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00006-9"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1098-2396(20001201)38:3<363::AID-SYN16>3.0.CO;2-A"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00180.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1331.2000.t01-1-00107.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)60328-3"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000080983"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.260"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-7378-1-4"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-0693-8_50"},{"key":"e_1_2_5_12_1","unstructured":"Christine C. Starr P.A. Larson P. Mah R. Eberling J. Jagust W.J. McGuire D.&Aminoff M.J.(2006) Aromatic L\u2010amino acid decarboxylase gene transfer therapy for Parkinson's disease: initial results of an open\u2010label dose escalation safety and tolerability study. In Abstracts of the American Academy of Neurology Annual Meeting. San Diego CA. S23.005."},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.06.005"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029285"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.11.031"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0270(01)00359-4"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(02)00009-6"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300010"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01716-X"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(84)90521-1"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05469.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1179\/147683009X423364"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.11.009"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(92)90256-Q"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21503"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000110348"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.10.089"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.09.019"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.04925.x"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.08.001"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21032"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.15.8138"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000320027"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1101\/lm.5.4.289","article-title":"Hyperactivity and learning deficits in transgenic mice bearing a human mutant thyroid hormone \u03b21 receptor gene","volume":"5","author":"McDonald M.P.","year":"1998","journal-title":"Learn Mem"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008877-200111000-00009"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2005.10.002"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0158"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8986"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl326"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.104257"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2007.03.001"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2127"},{"key":"e_1_2_5_43_1","first-page":"255","article-title":"Effects of chronic GM1 ganglioside treatment on cognitive and motor deficits in a slowly progressing model of Parkinsonism in non\u2010human primates","volume":"12","author":"Pope\u2010Coleman A.","year":"1998","journal-title":"Restor Neurol Neurosci"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(200005)36:2<120::AID-SYN5>3.0.CO;2-Y"},{"key":"e_1_2_5_45_1","first-page":"1","article-title":"Carbidopa\/levodopa\/entacapone: the evidence for its place in the treatment of Parkinson's disease","volume":"5","author":"Poulopoulos M.","year":"2010","journal-title":"Core Evid"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00183.x"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.07.004"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2004.07.027"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2009.06.017"},{"key":"e_1_2_5_50_1","first-page":"374","article-title":"A temporal evaluation of cytokines in rats after blast exposure","volume":"48","author":"Sajja V.S.","year":"2012","journal-title":"Biomed Sci Instrum"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-170"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-348"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.4.748"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(89)90117-9"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)01007-5"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00309-6"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0024-5"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2005.00161.x"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01361-6"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2010.09.003"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.PDR.0000155760.88664.06"},{"key":"e_1_2_5_62_1","unstructured":"Starr P.A. Verhagen L. Larson P.S. Bakay R. Taylor R. Cahn\u2010Weiner D. Bartus R. Ostrem J.L.&Marks W.J.J.(2007) Intrastriatal gene transfer with AAV\u2010neurturin for Parkinson's disease: results of a phase I trial. In Abstracts of the American Association of Neurological Surgeons Annual Meeting. Washington DC. Article ID 40735."},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0272-6"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2011.052"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2012.01.006"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3849"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1039"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)90033-3"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318330-000000000-00000"},{"key":"e_1_2_5_70_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.33549\/physiolres.931704","article-title":"Increased expression of erythropoietin receptor in 1\u2010methyl\u20104\u2010phenyl\u20101, 2, 3, 6\u2010tetrahydropyridine\u2010induced Parkinsonian model","volume":"59","author":"Wu Y.","year":"2010","journal-title":"Physiol Res"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1820"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.07.046"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2011.648761"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(90)90112-N"}],"container-title":["Genes, Brain and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fgbb.12001","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/gbb.12001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T03:35:38Z","timestamp":1698636938000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/gbb.12001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,28]]},"references-count":73,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1111\/gbb.12001"],"URL":"https:\/\/doi.org\/10.1111\/gbb.12001","archive":["Portico"],"relation":{},"ISSN":["1601-1848","1601-183X"],"issn-type":[{"value":"1601-1848","type":"print"},{"value":"1601-183X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,28]]}}}