Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (10): 4865-4875.doi: 10.4103/NRR.NRR-D-25-00324

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Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration. 

Qingying Yu1, 2, #, Zhaoyu Chen1, #, Jing Zhang3, #, Yu Cao4, Mengjia Sun2, Shuyi Ye2, Yike Huang5, Junchi He5, Liping Wang2, Kejian Li6, Simeng Gu7, Peng Sun1, *, **, Qingjun Zhu1, *, Fushun Wang8, *, Ning Weng3, *, Jason H. Huang9, 10, *   

  1. 1Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China; 
    2School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China; 
    3Department of Chinese Medicine, Shandong Mental Health Center, Shandong University, Jinan, Shandong Province, China; 
    4Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, Shandong Province, China; 
    5Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA; 
    6High-Level Key Disciplines of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China; 
    7Department of Medical Psychology, Jiangsu University Medical School, Zhenjiang, Jiangsu Province, China; 
    8Department of Psychology, Sichuan Normal University, Chengdu, Sichuan Province, China; 
    9Department of Neurosurgery, Baylor Scott & White Health Center, Temple, TX, USA; 
    10Department of Neurosurgery, Baylor College of Medicine, Temple, TX, USA
  • Online:2026-10-15 Published:2026-06-12
  • Contact: Peng Sun, PhD, sunpeng@sdutcm.edu.cn; Qingjun Zhu, PhD, zhuqingjun@sdutcm.edu.cn; Fushun Wang, PhD, 13814541138@163.com; Ning Weng, PhD, Wengning36@outlook.com; Jason H. Huang, MD, Jason.Huang@BSWHealth.org.
  • Supported by:
    This work was funded by Shandong Province Traditional Chinese Medicine Technology Development Project, Nos. M-2022198 and 2020Q040; the Natural Science Foundation of Shandong Province, Nos. ZR2020MB108 and ZR2019MH063; the Central Government Guided Local Science and Technology Development Project, No. 22-1-3-11-zyyd-nsh; Shandong Province Integrated Traditional Chinese and Western Medicine Depression Prevention and Treatment Project, No. YXH2019ZXY006; and the National Nature Science Foundation of China, No. 82171392 (to PS).

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Abstract: Major depressive disorder is a complex psychiatric condition characterized by mood dysregulation, cognitive impairment, and somatic symptoms. Recent studies underscore the pivotal roles of neural regeneration and inflammation in its pathophysiology. This narrative review synthesizes emerging evidence linking neuroinflammatory pathways and impaired neurogenesis in major depressive disorder. We explore mechanisms including microglial activation, kynurenine pathway dysregulation, synaptic remodeling, and gut–brain axis alterations. Special emphasis is placed on recent discoveries highlighting molecular cross-talk between immune responses and neural plasticity. By mapping these interactions, we aim to advance understanding of major depressive disorder subtypes and support the development of inflammation-targeted therapies.

Key words:  , inflammation, kynurenine, major depressive disorder, microglia, neural regeneration, neurogenesis, synaptic plasticity