{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:40:04Z","timestamp":1791330004204,"version":"4.3.1"},"reference-count":48,"publisher":"Society for Neuroscience","issue":"21","license":[{"start":{"date-parts":[[2007,11,23]],"date-time":"2007-11-23T00:00:00Z","timestamp":1195776000000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2007,5,23]]},"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is characterized by motoneuron (MN) degeneration, generalized weakness, and muscle atrophy. The premature death of MNs is thought to be a determinant in the onset of this disease. In a transgenic mouse model of ALS expressing the G86R mutant superoxide dismutase 1 (mSOD1), we demonstrated previously that CREB (cAMP response element-binding protein)-binding protein (CBP) and histone acetylation levels were specifically decreased in nuclei of degenerating MNs. We show here that oxidative stress and mSOD1 overexpression can both impinge on CBP levels by transcriptional repression, in an MN-derived cell line. Histone deacetylase inhibitor (HDACi) treatment was able to reset proper acetylation levels and displayed an efficient neuroprotective capacity against oxidative stress<jats:italic>in vitro<\/jats:italic>. Interestingly, HDACi also upregulated CBP transcriptional expression in MNs. Moreover, when injected to G86R mice<jats:italic>in vivo<\/jats:italic>, the HDACi sodium valproate (VPA) maintained normal acetylation levels in the spinal cord, efficiently restored CBP levels in MNs, and significantly prevented MN death in these animals. However, despite neuroprotection, mean survival of treated animals was not significantly improved (&lt;5%), and they died presenting the classical ALS symptoms. VPA was not able to prevent disruption of neuromuscular junctions, although it slightly delayed the onset of motor decline and retarded muscular atrophy to some extent. Together, these data show that neuroprotection can improve disease onset, but clearly provide evidence that one can uncouple MN survival from whole-animal survival and point to the neuromuscular junction perturbation as a primary event of ALS onset.<\/jats:p>","DOI":"10.1523\/jneurosci.1139-07.2007","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T23:18:51Z","timestamp":1179962331000},"page":"5535-5545","source":"Crossref","is-referenced-by-count":195,"title":["Sodium Valproate Exerts Neuroprotective Effects<i>In Vivo<\/i>through CREB-Binding Protein-Dependent Mechanisms But Does Not Improve Survival in an Amyotrophic Lateral Sclerosis Mouse Model"],"prefix":"10.1523","volume":"27","author":[{"given":"Caroline","family":"Rouaux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Panteleeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9rique","family":"Ren\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose-Luis","family":"Gonzalez de Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andoni","family":"Echaniz-Laguna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Dupuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Menger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Laurence","family":"Boutillier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Loeffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,5,23]]},"reference":[{"key":"2023041303253570000_27.21.5535.1","doi-asserted-by":"publisher","DOI":"10.1080\/14660820310011700"},{"key":"2023041303253570000_27.21.5535.2","doi-asserted-by":"publisher","DOI":"10.1038\/384641a0"},{"key":"2023041303253570000_27.21.5535.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199403033300901"},{"key":"2023041303253570000_27.21.5535.4","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1984.04050170073021"},{"key":"2023041303253570000_27.21.5535.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1123511"},{"key":"2023041303253570000_27.21.5535.6","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001940306"},{"key":"2023041303253570000_27.21.5535.7","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1046\/j.1471-4159.1998.70020501.x","article-title":"Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma x spinal cord cell line: role of poly (ADP-ribose) polymerase","volume":"70","author":"Cookson","year":"1998","journal-title":"J Neurochem"},{"key":"2023041303253570000_27.21.5535.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.12.023"},{"key":"2023041303253570000_27.21.5535.9","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0292"},{"key":"2023041303253570000_27.21.5535.10","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1182fje"},{"key":"2023041303253570000_27.21.5535.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402026101"},{"key":"2023041303253570000_27.21.5535.12","doi-asserted-by":"crossref","first-page":"9418","DOI":"10.1523\/JNEUROSCI.23-28-09418.2003","article-title":"Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice","volume":"23","author":"Ferrante","year":"2003","journal-title":"J Neurosci"},{"key":"2023041303253570000_27.21.5535.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2003.10.004"},{"key":"2023041303253570000_27.21.5535.14","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1523\/JNEUROSCI.20-02-00660.2000","article-title":"Restricted expression of G86R Cu\/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration","volume":"20","author":"Gong","year":"2000","journal-title":"J Neurosci"},{"key":"2023041303253570000_27.21.5535.15","doi-asserted-by":"crossref","unstructured":"Gonzalez de Aguilar JL Echaniz-Laguna A Fergani A Rene F Meininger V Loeffler JP Dupuis L (2007) Amyotrophic lateral sclerosis: all roads lead to Rome. 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