{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T16:07:23Z","timestamp":1782835643060,"version":"3.54.5"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2007,3,23]],"date-time":"2007-03-23T00:00:00Z","timestamp":1174608000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Apoptosis, a cell death mechanism regulated by Bcl\u20102 family members, has been proposed as one of the mechanisms leading to neuronal loss in Huntington's disease (HD). Here we examined the regulation of Bcl\u20102 family proteins in three different mouse models of HD with exon 1 mutant huntingtin: the R6\/1, the R6\/1:BDNF+\/\u2212, and the Tet\/HD94 in which the huntingtin transgene is controlled by the tetracycline\u2010inducible system. Our results disclosed an increase in the levels of the BH3\u2010only proteins Bid and Bim<jats:sub>EL<\/jats:sub> in the striatum of HD mouse models that was different depending on the stage of the disease. At 16 weeks of age, Bid was similarly enhanced in the striatum of R6\/1 and R6\/1:BDNF+\/\u2212 mice, whereas Bim<jats:sub>EL<\/jats:sub> protein levels were enhanced only in R6\/1:BDNF+\/\u2212 mice. In contrast, at later stages of the disease, both genotypes displayed increased levels of Bid and Bim<jats:sub>EL<\/jats:sub> proteins. Furthermore, Bax, Bak, Bad, Bcl\u20102, and Bcl\u2010x<jats:sub>L<\/jats:sub> proteins were not modified in any of the points analyzed. We next explored the potential reversibility of this phenomenon by analyzing conditional Tet\/HD94 mice. Constitutive expression of the transgene resulted in increased levels of Bid and Bim<jats:sub>EL<\/jats:sub> proteins, and only the Bid protein returned to wild\u2010type levels 5 months after mutant huntingtin shutdown. In conclusion, our results show that enhanced Bid protein levels represent an early mechanism linked to the continuous expression of mutant huntingtin that, together with enhanced Bim<jats:sub>EL<\/jats:sub>, may be a reporter of the progress and severity of neuronal dysfunction. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21258","type":"journal-article","created":{"date-parts":[[2007,3,26]],"date-time":"2007-03-26T18:40:41Z","timestamp":1174934441000},"page":"2756-2769","source":"Crossref","is-referenced-by-count":29,"title":["BH3\u2010only proteins Bid and Bim<sub>EL<\/sub> are differentially involved in neuronal dysfunction in mouse models of Huntington's disease"],"prefix":"10.1002","volume":"85","author":[{"given":"Juan M.","family":"Garc\u00eda\u2010Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"P\u00e9rez\u2010Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Xifr\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Canals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"D\u00edaz\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Trioulier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Brouillet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 J.","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Alberch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,3,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.06.005"},{"key":"e_1_2_6_3_1","volume-title":"Huntington's disease","author":"Bates GP","year":"2002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01584-8"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1477"},{"key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1523\/JNEUROSCI.16-17-05523.1996","article-title":"Expression of normal and mutant huntingtin in the developing brain","volume":"16","author":"Bhide PG","year":"1996","journal-title":"J Neurosci"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1197-04.2004"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc883"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198809000-00003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3183-05.2005"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199505090-00026"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/368147a0"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(03)00005-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401995"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.09.013"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.018"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.04590.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207521"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406837101"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00187-2"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-19-07268.2000"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900222"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401688"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1998.0709"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858404266777"},{"key":"e_1_2_6_27_1","article-title":"Down\u2010regulation of Bim by brain\u2010derived neurotrophic factor activation of TrkB protects neuroblastoma cells from paclitaxel but not ectoposide or cisplatin\u2010induced cell death","author":"Li Z","year":"2006","journal-title":"Cell Death Differ"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80085-9"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0528"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81369-0"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00230496"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198611133152006"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64557-9"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02904.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.7006"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02572.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03775.1995"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505546200"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025682611389"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210296200"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001090100223"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401227"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-259"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/17135"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1995.1029"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.09.038"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.19.2799"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-004-0957-5"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"e_1_2_6_50_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1023\/B:JOBB.0000041756.23918.11","article-title":"Neuronal apoptosis: BH3\u2010only proteins the real killers?","volume":"36","author":"Ward MW","year":"2004","journal-title":"J Bioenerg Biomembr"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511562200"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03935.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207516200"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80623-6"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1761"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01980.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02105.x"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80501-2"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059581"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1219"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.21258","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.21258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T23:18:31Z","timestamp":1694647111000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.21258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3,23]]},"references-count":59,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2007,9]]}},"alternative-id":["10.1002\/jnr.21258"],"URL":"https:\/\/doi.org\/10.1002\/jnr.21258","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3,23]]}}}