Dr. Huang, Yi-Shuian 's orcid link picture Dr. Huang, Yi-Shuian 's publons link picture Dr. Huang, Yi-Shuian 's Personal Homepage Dr. Huang, Yi-Shuian 's Youtube

Dr. Huang, Yi-Shuian

Research Fellow
Division Chief
  • 02-2789-9174 (Lab) (Room No: N703)
  • 02-2652-3523 (Office)

  • Translational Control/ RNA 轉譯調控
  • Cap modification/ RNA-cap 修飾調控
  • Molecular & Cellular Neuroscience/ 分子與細胞神經生物學

Education and Positions:
  • Ph.D. University of Texas Southwestern Medical Center at Dallas

Highlight Detail

CPEB3-downregulated Nr3c1 mRNA translation confers resilience to developing posttraumatic stress disorder-like behavior in fear-conditioned mice

Dr. Huang, Yi-Shuian
Neuropsychopharmacology, May 03, 2021



Susceptibility or resilience to posttraumatic stress disorder (PTSD) depends on one's ability to appropriately adjust synaptic plasticity for coping with the traumatic experience. Activity-regulated mRNA translation synthesizes plasticity-related proteins to support long-term synaptic changes and memory. Hence, cytoplasmic polyadenylation element-binding protein 3-knockout (CPEB3-KO) mice, showing dysregulated translation-associated synaptic rigidity, may be susceptible to PTSD-like behavior. Here, using a context-dependent auditory fear conditioning and extinction paradigm, we found that CPEB3-KO mice exhibited traumatic intensity-dependent PTSD-like fear memory. A genome-wide screen of CPEB3-bound transcripts revealed that Nr3c1, encoding glucocorticoid receptor (GR), was translationally suppressed by CPEB3. Thus, CPEB3-KO neurons with elevated GR expression exhibited increased corticosterone-induced calcium influx and decreased mRNA and protein levels of brain-derived neurotrophic factor (Bdnf). Moreover, the reduced expression of BDNF was associated with increased GR level during fear extinction in CPEB3-KO hippocampi. Intracerebroventricular delivery of BDNF before extinction training mitigated spontaneous fear intrusion in CPEB3-KO mice during extinction recall. Analysis of two GEO datasets revealed decreased transcriptomic expression of CPEB3 but not NR3C1 in peripheral blood mononuclear cells of humans with PTSD. Collectively, this study reveals that CPEB3, as a potential PTSD-risk gene, downregulates Nr3c1 translation to maintain proper GR-BDNF signaling for fear extinction.