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Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats

Mampay, Myrthe; Velasco?Estevez, Mar�a; Rolle, Sara O.; Chaney, Aisling M.; Boutin, Herv�; Dev, Kumlesh K.; Moeendarbary, Emad; Sheridan, Graham K.

Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats Thumbnail


Authors

Myrthe Mampay

Mar�a Velasco?Estevez

Sara O. Rolle

Aisling M. Chaney

Herv� Boutin

Kumlesh K. Dev

Emad Moeendarbary



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 immunolocalisation 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 presynaptic 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 are 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.

Citation

Mampay, M., Velasco‐Estevez, M., Rolle, S. O., Chaney, A. M., Boutin, H., Dev, K. K., …Sheridan, G. K. (2021). Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer’s disease rats. FEBS Open Bio, 11(1), 146-163. https://doi.org/10.1002/2211-5463.13036

Journal Article Type Article
Acceptance Date Nov 4, 2020
Online Publication Date Nov 13, 2020
Publication Date 2021-01
Deposit Date Apr 12, 2021
Publicly Available Date Apr 23, 2021
Journal FEBS Open Bio
Electronic ISSN 2211-5463
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 11
Issue 1
Pages 146-163
DOI https://doi.org/10.1002/2211-5463.13036
Keywords General Biochemistry, Genetics and Molecular Biology
Public URL https://nottingham-repository.worktribe.com/output/5040411
Publisher URL https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.13036
Additional Information Received: 2020-07-25; Accepted: 2020-11-11; Published: 2020-11-13

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