Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer's disease rats
| Autor: | Graham K. Sheridan, Maria Velasco-Estevez, Kumlesh K. Dev, Aisling Chaney, Hervé Boutin, Myrthe Mampay, Emad Moeendarbary, Sara O. Rolle |
|---|---|
| Přispěvatelé: | Basic (bio-) Medical Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine hippocampus Synaptophysin Hippocampus Hippocampal formation Biology Neuroprotection General Biochemistry Genetics and Molecular Biology Healthy Aging Amyloid beta-Protein Precursor 03 medical and health sciences Spatio-Temporal Analysis 0302 clinical medicine synapse Alzheimer Disease Memory Presenilin-1 medicine Animals Humans Learning CA1 Region Hippocampal Research Articles Rest (music) Neurons REST Neurodegeneration Subiculum medicine.disease TgF344‐AD rats Rats Inbred F344 Frontal Lobe Rats Repressor Proteins Disease Models Animal 030104 developmental biology medicine.anatomical_structure nervous system ageing Ageing 030220 oncology & carcinogenesis Mutation Female Neuron Rats Transgenic Alzheimer’s disease Neuroscience Research Article |
| Zdroj: | Mampay, M, Velasco-Estevez, M, Rolle, S O, Chaney, A M, Boutin, H, Dev, K K, Moeendarbary, E & Sheridan, G K 2021, ' Spatiotemporal immunolocalisation of REST in the brain of healthy ageing and Alzheimer's disease rats ', FEBS open bio . https://doi.org/10.1002/2211-5463.13036 FEBS Open Bio |
| DOI: | 10.1002/2211-5463.13036 |
| Popis: | Upregulation of the transcription factor, REST, is neuroprotective in the ageing brain. We quantified changes in nuclear REST expression in the brains of ageing wild‐type (WT) and Alzheimer’s disease (AD) rats. REST increased in structures involved in learning and memory in WT but not AD rats, potentially explaining why these regions are vulnerable to synapse loss, neuroinflammation and astrogliosis. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|