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Spatiotemporal immunolocalization of REST in the brain of healthy ageing and Alzheimer's disease rats

Mampay, M; Velasco-Estevez, M; Rolle, SO; Chaney, AM; Boutin, H; Dev, KK; Moeendarbary, E; (2020) Spatiotemporal immunolocalization of REST in the brain of healthy ageing and Alzheimer's disease rats. FEBS Open Bio 10.1002/2211-5463.13036. (In press). Green open access

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Abstract

In the brain, REST (Repressor Element‐1 Silencing Transcription factor) is a key regulator of neuron cell‐specific 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’s disease (AD) pathology. Hippocampal and cortical neurons are known to be particularly susceptible to AD‐associated neurodegeneration. However, REST expression has not been extensively characterised in the healthy ageing brain. Here, we examined the spatiotemporal immunolocalization of REST in the brains of healthy ageing wild‐type Fischer‐344 and transgenic Alzheimer’s disease rats (TgF344‐AD). Nuclear expression of REST increased from 6‐months to 18‐months of age in the hippocampus, frontal cortex, and subiculum of wild‐type rats, but not in TgF344‐AD rats. No changes in REST were measured in more posterior cortical regions or in the thalamus. Interestingly, levels of the pre‐synaptic marker synaptophysin, a known gene target of REST, were lower in CA1 hippocampal neurons of 18‐month TgF344‐AD rats compared to 18‐month wild‐types, suggesting that elevated nuclear REST may protect against synapse loss in the CA1 of 18‐month wild‐type rats. High REST expression in ageing wild‐type 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 is context‐, age‐, and brain region‐specific. Moreover, key brain structures involved in learning and memory display elevated REST expression in healthy ageing wild‐type rats but not TgF344‐AD rats.

Type: Article
Title: Spatiotemporal immunolocalization of REST in the brain of healthy ageing and Alzheimer's disease rats
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/2211-5463.13036
Publisher version: https://doi.org/10.1002/2211-5463.13036
Language: English
Additional information: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Keywords: Ageing, Alzheimer’s disease, REST, TgF344-AD rats, hippocampus, synapse
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10115980
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