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Epidemiologic studies in humans and research in rodents have suggested that hypothyroidism could participate in the etiology of AD. Recently, we reported that adult\u2010onset hypothyroidism in rats favors \u03b2\u2010amyloid peptide production in the hippocampus. Here, using the same hypothyroidism model with the antithyroid molecule propythiouracyl (PTU), we further explored AD\u2010related features, dysfunctional cell\u2010signaling mechanisms and hippocampal\u2010dependent learning and memory. <jats:italic>In vivo<\/jats:italic> MRI revealed a progressive decrease in cerebral volume of PTU\u2010treated rats. In the hippocampus, hypothyroidism resulted in tau hyperphosphorylation and increases in several proinflammatory cytokines. These modifications were associated with impaired spatial memory and reduced hippocampal expression of signaling molecules important for synaptic plasticity and memory, including neurogranin, CaMKII, ERK, GSK3\u03b2, CREB, and expression of the transcription factor EGR1\/Zif268. These data strengthen the idea that hypothyroidism represents an important factor influencing the risk of developing sporadic forms of AD. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22319","type":"journal-article","created":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T01:01:56Z","timestamp":1404176516000},"page":"1381-1393","source":"Crossref","is-referenced-by-count":67,"title":["PTU\u2010induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer's disease in the hippocampus and spatial memory impairments"],"prefix":"10.1002","volume":"24","author":[{"given":"Amina","family":"Chaalal","sequence":"first","affiliation":[{"name":"Centre de Neurosciences Paris\u2010Sud CNRS UMR 8195 F\u201091405 Orsay France"},{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseline","family":"Poirier","sequence":"additional","affiliation":[{"name":"Centre de Neurosciences Paris\u2010Sud CNRS UMR 8195 F\u201091405 Orsay France"},{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Blum","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille\u2010Nord de France UDSL F\u201059000 Lille France"},{"name":"Inserm U837, Centre de recherche Jean\u2010Pierre Aubert IMPRT F\u201059000 Lille France"},{"name":"CHRU\u2010Lille F\u201059000 Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Gillet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"},{"name":"Imagerie par R\u00e9sonance Magn\u00e9tique M\u00e9dicale et MultiModalit\u00e9 CNRS\u2010UMR8081 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Le Blanc","sequence":"additional","affiliation":[{"name":"Centre de Neurosciences Paris\u2010Sud CNRS UMR 8195 F\u201091405 Orsay France"},{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Basquin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille\u2010Nord de France UDSL F\u201059000 Lille France"},{"name":"Inserm U837, Centre de recherche Jean\u2010Pierre Aubert IMPRT F\u201059000 Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Bu\u00e9e","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Lille\u2010Nord de France UDSL F\u201059000 Lille France"},{"name":"Inserm U837, Centre de recherche Jean\u2010Pierre Aubert IMPRT F\u201059000 Lille France"},{"name":"CHRU\u2010Lille F\u201059000 Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Laroche","sequence":"additional","affiliation":[{"name":"Centre de Neurosciences Paris\u2010Sud CNRS UMR 8195 F\u201091405 Orsay France"},{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Enderlin","sequence":"additional","affiliation":[{"name":"Centre de Neurosciences Paris\u2010Sud CNRS UMR 8195 F\u201091405 Orsay France"},{"name":"Universit\u00e9 Paris\u2010Sud UMR 8195 F\u201091405 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,22]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1","article-title":"Thyroid and aging or the aging thyroid?","volume":"2013","author":"Aggarwal N","year":"2013","journal-title":"An evidence\u2010based analysis of the literature. 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