Correlation Engine 2.0
Clear Search sequence regions


  • AMPA (1)
  • brain (2)
  • Fxr1 (8)
  • Fxr1h (1)
  • gene (3)
  • gene knockout techniques (1)
  • GSK3β (1)
  • homeostasis (2)
  • lithium (1)
  • mice (2)
  • mice knockout (1)
  • neurons (1)
  • receptors (1)
  • receptors ampa (3)
  • regulates (1)
  • rna (2)
  • schizophrenia (1)
  • sleep (8)
  • system- processes (1)
  • Sizes of these terms reflect their relevance to your search.

    The fragile X autosomal homolog 1 (Fxr1) is regulated by lithium and has been GWAS-associated with schizophrenia and insomnia. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and involves both cell-autonomous and system-level processes such as sleep. We examined the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and neuronal responses to sleep loss, using a combination of gene overexpression and Crispr/Cas9-mediated somatic knockouts to modulate gene expression. Our findings indicate that Fxr1 is downregulated during both scaling and sleep deprivation via a glycogen synthase kinase 3 beta (GSK3β)-dependent mechanism. In both conditions, downregulation of Fxr1 is essential for the homeostatic modulation of surface AMPA receptors and synaptic strength. Preventing the downregulation of Fxr1 during sleep deprivation results in altered EEG signatures. Furthermore, sequencing of neuronal translatomes revealed the contribution of Fxr1 to changes induced by sleep deprivation. These findings uncover a role of Fxr1 as a shared signaling hub between cell-autonomous homeostatic plasticity and system-level responses to sleep loss, with potential implications for neuropsychiatric illnesses and treatments. © 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

    Citation

    Jivan Khlghatyan, Alesya Evstratova, Lusine Bozoyan, Simon Chamberland, Dipashree Chatterjee, Aleksandra Marakhovskaia, Tiago Soares Silva, Katalin Toth, Valerie Mongrain, Jean-Martin Beaulieu. Fxr1 regulates sleep and synaptic homeostasis. The EMBO journal. 2020 Nov 02;39(21):e103864

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 32893934

    View Full Text