{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T19:05:53Z","timestamp":1771268753574,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["RPG\u20102018\u2010443"],"award-info":[{"award-number":["RPG\u20102018\u2010443"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>In the brain, REST (Repressor Element\u20101 Silencing Transcription factor) is a key regulator of neuron cell\u2010specific gene expression. Nuclear translocation of neuronal REST has been shown to be neuroprotective in a healthy ageing context. In contrast, inability to upregulate nuclear REST is thought to leave ageing neurons vulnerable to neurodegenerative stimuli, such as Alzheimer\u2019s disease (AD) pathology. Hippocampal and cortical neurons are known to be particularly susceptible to AD\u2010associated neurodegeneration. However, REST expression has not been extensively characterised in the healthy ageing brain. Here, we examined the spatiotemporal immunolocalisation of REST in the brains of healthy ageing wild\u2010type Fischer\u2010344 and transgenic Alzheimer\u2019s disease rats (TgF344\u2010AD). Nuclear expression of REST increased from 6\u00a0months to 18\u00a0months of age in the hippocampus, frontal cortex and subiculum of wild\u2010type rats, but not in TgF344\u2010AD rats. No changes in REST were measured in more posterior cortical regions or in the thalamus. Interestingly, levels of the presynaptic marker synaptophysin, a known gene target of REST, were lower in CA1 hippocampal neurons of 18\u2010month TgF344\u2010AD rats compared to 18\u2010month wild\u2010types, suggesting that elevated nuclear REST may protect against synapse loss in the CA1 of 18\u2010month wild\u2010type rats. High REST expression in ageing wild\u2010type rats did not, however, protect against axonal loss nor against astroglial reactivity in the hippocampus. Taken together, our data confirm that changes in nuclear REST expression are context\u2010, age\u2010 and brain region\u2010specific. Moreover, key brain structures involved in learning and memory display elevated REST expression in healthy ageing wild\u2010type rats but not TgF344\u2010AD rats.<\/jats:p>","DOI":"10.1002\/2211-5463.13036","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T08:41:26Z","timestamp":1605256886000},"page":"146-163","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer\u2019s disease rats"],"prefix":"10.1002","volume":"11","author":[{"given":"Myrthe","family":"Mampay","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences University of Brighton 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