Distinct regulation of hippocampal neuroplasticity and ciliary genes by corticosteroid receptors

Autor: Silvia Salatino, Clare L. M. Kennedy, Karen R. Mifsud, Johannes M. H. M. Reul, Samantha N. Haque, Eshita Sharma, Oscar Cordero Llana, Polina Panchenko, John Broxholme, Simon Engledow, Hannah M Goss, Andriana Gialeli, Emily M. Price, Helen Lockstone
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-23 (2021)
Nature Communications
Mifsud, K R, Kennedy, C L M, Salatino, S, Sharma, E, Price, E M, Haque, S N, Gialeli, A, Goss, H M, Panchenko, P E, Broxholme, J, Engledow, S, Lockstone, H, Cordero Llana, O & Reul, J M H M 2021, ' Distinct regulation of hippocampal neuroplasticity and ciliary genes by corticosteroid receptors ', Nature Communications, vol. 12, no. 1, 4737 . https://doi.org/10.1038/s41467-021-24967-z
ISSN: 2041-1723
DOI: 10.1038/s41467-021-24967-z
Popis: Glucocorticoid hormones (GCs) — acting through hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) — are critical to physiological regulation and behavioural adaptation. We conducted genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus to elucidate MR- and GR-regulated genes under circadian variation or acute stress. In a subset of genes, these physiological conditions resulted in enhanced MR and/or GR binding to DNA sequences and associated transcriptional changes. Binding of MR at a substantial number of sites however remained unchanged. MR and GR binding occur at overlapping as well as distinct loci. Moreover, although the GC response element (GRE) was the predominant motif, the transcription factor recognition site composition within MR and GR binding peaks show marked differences. Pathway analysis uncovered that MR and GR regulate a substantial number of genes involved in synaptic/neuro-plasticity, cell morphology and development, behavior, and neuropsychiatric disorders. We find that MR, not GR, is the predominant receptor binding to >50 ciliary genes; and that MR function is linked to neuronal differentiation and ciliogenesis in human fetal neuronal progenitor cells. These results show that hippocampal MRs and GRs constitutively and dynamically regulate genomic activities underpinning neuronal plasticity and behavioral adaptation to changing environments.
Glucocorticoid hormones (GCs) are of critical importance for maintaining brain health, but their involvement in mental disorders is poorly understood. Here the authors show how GCs act through hippocampal mineralocorticoid and glucocorticoid receptors to impact the gene regulatory programs underpinning neuronal plasticity, ciliogenesis and behavioral adaptation.
Databáze: OpenAIRE
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