Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (1): 159-173.doi: 10.4103/NRR.NRR-D-23-01419

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Brain region–specific roles of brain-derived neurotrophic factor in social stress–induced depressive-like behavior

Man Han1, 2, 3, Deyang Zeng1, 2, 3, Wei Tan2, Xingxing Chen1, 2, 3, Shuyuan Bai1, 2, 3, Qiong Wu1, 2, 3, Yushan Chen1, 2, 3, Zhen Wei1, 2, 3, Yufei Mei1, 2, 3, Yan Zeng1, 2, 3, *   

  1. 1Brain Science and Advanced Technology Institute, Wuhan University of Science and Technology, Wuhan, Hubei Province, China; 2Geriatric Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei Province, China; 3School of Public Health, Wuhan University of Science and Technology, Wuhan, Hubei Province, China
  • Online:2025-01-15 Published:1900-01-01
  • Contact: Yan Zeng, PhD, zengyan68@wust.edu.cn.
  • Supported by:
    This work was supported financially by the National Natural Science Foundation of China, No. 82071272 (to YZ).

Abstract: Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Key words: amygdala, chronic mild stress, chronic social defeat stress, corticolimbic system, depression, hippocampus, medial prefrontal cortex, nucleus accumbens, social stress models, ventral tegmental area