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This study asked whether up-regulating endogenous BDNF levels with an ampakine, a positive modulator of AMPA-type glutamate receptors, rescues plasticity and reduces learning problems in HD (CAG140) mice. Twice-daily injections of a short half-life ampakine normalized BDNF levels, activity-driven actin polymerization in dendritic spines, and LTP stabilization in 8-week-old mutants. Comparable results were obtained in 16-week-old HD mice with more severe LTP deficits. Ampakine treatments had no measurable effect on the decreased locomotor activity observed in the mutants but offset their impairments in long-term memory. Given that ampakines are well tolerated in clinical trials and were effective in this study after brief exposures, these results suggest a novel strategy for chronic treatment of the cognitive difficulties that occur in the early stages of HD.<\/jats:p>","DOI":"10.1073\/pnas.0811228106","type":"journal-article","created":{"date-parts":[[2009,3,6]],"date-time":"2009-03-06T00:07:58Z","timestamp":1236298078000},"page":"4906-4911","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":248,"title":["Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington's disease knockin mice"],"prefix":"10.1073","volume":"106","author":[{"given":"Danielle A.","family":"Simmons","sequence":"first","affiliation":[{"name":"Departments of aPsychiatry and Human Behavior,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Rex","sequence":"additional","affiliation":[{"name":"Neurobiology and Behavior, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Philosophy, Carnegie Mellon University, Pittsburgh, PA 15217"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Pandyarajan","sequence":"additional","affiliation":[{"name":"Anatomy and Neurobiology, University of California, Irvine, CA 92617-4291; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Fedulov","sequence":"additional","affiliation":[{"name":"Anatomy and Neurobiology, University of California, Irvine, CA 92617-4291; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Gall","sequence":"additional","affiliation":[{"name":"Neurobiology and Behavior, and"},{"name":"Anatomy and Neurobiology, University of California, Irvine, CA 92617-4291; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Lynch","sequence":"additional","affiliation":[{"name":"Departments of aPsychiatry and Human Behavior,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000098878.47789.BD"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.6.773"},{"key":"e_1_3_3_5_2","first-page":"1329","article-title":"Evidence for specific cognitive deficits in preclinical Huntington's disease","volume":"121","author":"Lawrence A","year":"1998","unstructured":"A Lawrence, et al., Evidence for specific cognitive deficits in preclinical Huntington's disease. 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