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One especially notable and relatively common circadian disturbance among the aged is \u201csundowning syndrome,\u201d which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome.<\/jats:p>","DOI":"10.1073\/pnas.1103098108","type":"journal-article","created":{"date-parts":[[2011,6,28]],"date-time":"2011-06-28T05:22:51Z","timestamp":1309238571000},"page":"11686-11691","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":73,"title":["Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice"],"prefix":"10.1073","volume":"108","author":[{"given":"Tracy A.","family":"Bedrosian","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Institute for Behavioral Medicine Research, Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamillya L.","family":"Herring","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Behavioral Medicine Research, Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary M.","family":"Weil","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Behavioral Medicine Research, Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Institute for Behavioral Medicine Research, Ohio State University Medical Center, Columbus, OH 43210"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,6,27]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2006.11.010"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(00)00191-1"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/18.6.425"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000103735"},{"key":"e_1_3_3_5_2","first-page":"168","article-title":"Sundowning and circadian rhythm disorders in dementia","volume":"106","author":"Klaffke S","year":"2006","unstructured":"S Klaffke, J Staedt, Sundowning and circadian rhythm disorders in dementia. 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