Molecular and Cellular Determinant for Stress-Induced Depression

Seminar

  • Date: Feb 20, 2019
  • Time: 12:00 - 13:00
  • Speaker: Ji-Seon Seo
  • Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA
  • Location: Max Planck Institute of Psychiatry
  • Room: Large Lecture Hall
  • Host: Elisabeth Binder | Alon Chen
  • Contact: info@psych.mpg.de
Molecular and Cellular Determinant for Stress-Induced Depression<i></i>
Chronic stress plays a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC leading to stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein which binds to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents.

In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2+) glutamatergic neurons. Viral expression of p11 in D2+ PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2+ neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2+ PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, providing a framework for the development of new strategies to treat stress-associated mental illnesses.

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