2. Academic Validation
  3. PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice

PTEN in prefrontal cortex is essential in regulating depression-like behaviors in mice

  • Transl Psychiatry. 2021 Mar 26;11(1):185. doi: 10.1038/s41398-021-01312-y.
Xiao-Qing Wang 1,  Lei Zhang 2 3,  Zhong-Yuan Xia 4,  Jia-Yin Chen 1 5,  Yiru Fang 6 7,  Yu-Qiang Ding 8 9 10
Affiliations

Affiliations

  • 1 Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, 200092, China.
  • 2 Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, 200092, China. leizhang1120@outlook.com.
  • 3 Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. leizhang1120@outlook.com.
  • 4 Shanghai Tenth People's Hospital, Clinical Medical School of Nanjing Medical University, Nanjing, 211166, China.
  • 5 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
  • 6 Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
  • 7 CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, 200031, China.
  • 8 Key Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, 200092, China. dingyuqiang@vip.163.com.
  • 9 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. dingyuqiang@vip.163.com.
  • 10 Department of Laboratory Animal Science, Fudan University, Shanghai, 200032, China. dingyuqiang@vip.163.com.
PMID: 33771972 DOI: 10.1038/s41398-021-01312-y
Abstract

Chronic stress is an environmental risk factor for depression and causes neuronal atrophy in the prefrontal cortex (PFC) and other brain regions. It is still unclear about the molecular mechanism underlying the behavioral alterations and neuronal atrophy induced by chronic stress. We here report that Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a mediator for chronic stress-induced depression-like behaviors and neuronal atrophy in mice. One-month chronic restraint stress (CRS) up-regulated PTEN signaling pathway in the PFC of mice as indicated by increasing levels of PTEN, p-MEK, and p-ERK but decreasing levels of p-AKT. Over-expression of PTEN in the PFC led to an increase of depression-like behaviors, whereas genetic inactivation or knockdown of PTEN in the PFC prevented the CRS-induced depression-like behaviors. In addition, systemic administration of PTEN Inhibitor was also able to prevent these behaviors. Cellular examination showed that PTEN over-expression or the CRS treatment resulted in PFC neuron atrophy, and this atrophy was blocked by genetic inactivation of PTEN or systemic administration of PTEN Inhibitor. Furthermore, possible causal link between PTEN and glucocorticoids was examined. In chronic dexamethasone (Dex, a glucocorticoid agonist) treatment-induced depression model, increased PTEN levels were observed, and depression-like behaviors and PFC neuron atrophy were attenuated by the administration of PTEN Inhibitor. Our results indicate that PTEN serves as a key mediator in chronic stress-induced neuron atrophy as well as depression-like behaviors, providing molecular evidence supporting the synaptic plasticity theory of depression.

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