Rxivist logo

Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits

By Renee J. Tamming, Vanessa Dumeaux, Luana Langlois, Jacob Ellegood, Lily R. Qiu, Yan Jiang, Jason P. Lerch, Nathalie G Bérubé

Posted 12 Apr 2019
bioRxiv DOI: 10.1101/606442 (published DOI: 10.1016/j.celrep.2020.107838)

Mutations in the ATRX chromatin remodeler are associated with syndromic and non-syndromic intellectual disability. Emerging evidence points to key roles for ATRX in preserving neuroprogenitor cell genomic stability, whereas ATRX function in differentiated neurons and memory processes are still unresolved. Here, we show that Atrx deletion in mouse forebrain glutamatergic neurons causes distinct hippocampal structural defects identified by magnetic resonance imaging. Ultrastructural analysis revealed fewer presynaptic vesicles and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. These synaptic defects are associated with impaired long-term contextual memory in male, but not female mice. Mechanistically, we identify ATRX-dependent and sex-specific alterations in synaptic gene expression linked to Mir137 levels, a known regulator of presynaptic processes and spatial memory. We conclude that ablation of Atrx in excitatory forebrain neurons leads to sexually dimorphic outcomes on miR-137 and on spatial memory, identifying a promising therapeutic target for neurological disorders caused by ATRX dysfunction. Summary statement Ablation of the ATRX chromatin remodeler specifically in forebrain excitatory neurons of mice causes male-specific deficits in long-term spatial memory associated with miR-137 overexpression, transcriptional changes and structural alterations corresponding to pre- and post-synaptic abnormalities.

Download data

  • Downloaded 543 times
  • Download rankings, all-time:
    • Site-wide: 68,707
    • In neuroscience: 9,957
  • Year to date:
    • Site-wide: 118,465
  • Since beginning of last month:
    • Site-wide: 98,353

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News