Transcriptional networks of resilience and susceptibility

Seminar

  • Date: Mar 21, 2019
  • Time: 01:00 PM - 02:00 PM (Local Time Germany)
  • Speaker: Dr Rosemary C. Bagot
  • Departments of Psychology & Psychiatry McGill University, Ludmer Centre Researcher, Montreal, Canada
  • Location: Max Planck Institute of Psychiatry
  • Room: Lecture Hall
  • Host: Dr Juan Pablo Lopez
  • Contact: jplopez@psych.mpg.de
Transcriptional networks of resilience and susceptibility
© @avogado6
Evidence in both humans and animals points to dysregulated circuit function in depression, but the molecular mechanisms are unknown. Recent functional studies suggest that opposing alterations in prefrontal cortex and ventral hippocampus regulate resilience and susceptibility to chronic social defeat stress (CSDS), a highly validated mouse model of depression.

Integrative network analysis of a large-scale RNA-sequencing data set from multiple brain regions in control, susceptible and resilient mice identified transcriptional networks that regulate susceptibility or resilience in distinct brain regions. In vivo manipulations of multiple key regulators confirmed the functional significance of these networks by assessing the effects of viral-mediated over-expression of identified network hub-genes in mice exposed to CSDS on depression associated behavioral assays, electrophysiological assays of synaptic function and transcriptional regulation of gene networks. These results demonstrate that states of resilience and susceptibility are driven by distinct circuit-level transcriptional networks and confirm the utility of a systems biology approach in identifying novel transcriptional mechanisms of stress susceptibility and resilience that may offer new targets to reverse susceptibility or induce resilience.

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