{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:12:47Z","timestamp":1780089167553,"version":"3.54.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,5,15]],"date-time":"2001-05-15T00:00:00Z","timestamp":989884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2001,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiotrophin\u20101 (CT\u20101) has potent survival\u2010promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT\u20101 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected CT\u20101 (1 mg\/kg, <jats:italic>n<\/jats:italic> = 18, in two experiments) or vehicle (<jats:italic>n<\/jats:italic> = 18, in two experiments) daily, 6 times\/week for 4 weeks after clinical diagnosis at age 3 to 4 weeks. Cardiotrophin\u20101 treatment prevented deterioration in paw position and walking pattern abnormalities. Grip strength declined steadily in the vehicle group, whereas in the CT\u20101 group it declined at week 1 but increased thereafter to exceed baseline strength by 5% (<jats:italic>P<\/jats:italic> = 0.0002) at week 4. Running speed was faster with CT\u20101 (<jats:italic>P<\/jats:italic> = 0.007). Biceps muscle twitch tension, muscle weight, mean muscle fiber diameter, and intramuscular axonal sprouting were significantly greater with CT\u20101 treatment than with vehicle treatment. Histometry revealed a trend that indicated CT\u20101 modestly increased the number of immunoreactive motor neurons, as determined by both choline acetyltransferase and c\u2010Ret antibodies, and reduced the number of phosphorylated neurofilament immunoreactive perikarya (<jats:italic>P<\/jats:italic> = 0.05). The number of large myelinated motor axons significantly increased with treatment (206 versus 113, <jats:italic>P<\/jats:italic> = 0.01). We conclude that CT\u20101 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND. \u00a9 2001 John Wiley &amp; Sons, Inc. Muscle Nerve 24: 769\u2013777, 2001<\/jats:p>","DOI":"10.1002\/mus.1068","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T22:08:54Z","timestamp":1030313334000},"page":"769-777","source":"Crossref","is-referenced-by-count":23,"title":["Effects of cardiotrophin\u20101 (CT\u20101) in a mouse motor neuron disease"],"prefix":"10.1002","volume":"24","author":[{"given":"Hiroshi","family":"Mitsumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Klinkosz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik P.","family":"Pioro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazufumi","family":"Tsuzaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Ishiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhona M.","family":"O'Leary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Pennica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,5,15]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1244"},{"key":"e_1_2_8_3_2","first-page":"63","article-title":"Studies on a murine form of spontaneous lower motor neuron degenerations: the wobbler (wr) mouse","volume":"76","author":"Andrew JM","year":"1974","journal-title":"Am J Pathol"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990101)55:1<119::AID-JNR13>3.0.CO;2-6"},{"key":"e_1_2_8_5_2","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1523\/JNEUROSCI.18-04-01440.1998","article-title":"Synergistic effects of schwann\u2010 and muscle\u2010derived factors on motoneuron survival involve GDNF and cardiotrophin\u20101 (CT\u20101)","volume":"18","author":"Arce V","year":"1998","journal-title":"J Neurosci"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1984.04050170073021"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6265"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.31.6.535"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.81524"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90113-9"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370413"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410370110"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90245-M"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(99)00004-5"},{"key":"e_1_2_8_15_2","first-page":"540A","article-title":"Glial cell line\u2013derived neurotrophic factor reduces motor dysfunction in wobbler mice","volume":"40","author":"Klinkosz B","year":"1996","journal-title":"Ann Neurol"},{"key":"e_1_2_8_16_2","first-page":"200","article-title":"The effects of daily administration of ciliary neurotrophic factor (CNTF) or brain\u2010derived neurotrophic factor (BDNF) in wobbler mice","volume":"20","author":"Klinkosz B","year":"1994","journal-title":"Soc Neurosci Abst"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/378724a0"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/105.4.811"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410190108"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360205"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8066451"},{"key":"e_1_2_8_22_2","first-page":"1705","article-title":"Cardiotrophin\u20101 has marked protective effects in wobbler mouse motor neuron disease","volume":"23","author":"Mitsumoto H","year":"1997","journal-title":"Soc Neurosc Abst"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/113.2.497"},{"key":"e_1_2_8_24_2","first-page":"9","article-title":"Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients","volume":"1988","author":"Munoz DG","journal-title":"J Neuropathol Exp Neurol"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-13-05429.1999"},{"key":"e_1_2_8_26_2","first-page":"281","article-title":"The absence of significant postnatal motoneuron death in the brachial and lumbar spinal cord of the rat","volume":"246","author":"Oppenheim RW","year":"1986","journal-title":"J Comp Anat"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.91.3.866"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80281-0"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1142"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.18.10915"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880010110"},{"key":"e_1_2_8_32_2","first-page":"375","article-title":"Animal models of ALS","volume":"3","author":"Pioro EP","year":"1996","journal-title":"Clin Neurosci"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199809140-00023"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900890"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.8.4855"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199105000-00002"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/358502a0"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.19.6126"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmus.1068","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.1068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T19:10:24Z","timestamp":1696792224000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.1068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,15]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,6]]}},"alternative-id":["10.1002\/mus.1068"],"URL":"https:\/\/doi.org\/10.1002\/mus.1068","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,15]]}}}