Regulatory Effects of Neuroinflammatory Responses Through Brain-Derived Neurotrophic Factor Signaling in Microglial Cells

  • Sheng-Wei Lai
  • Jia-Hong Chen
  • Hsiao-Yun Lin
  • Yu-Shu Liu
  • Cheng-Fang Tsai
  • Pei-Chun Chang
  • Dah-Yuu Lu
  • Chingju Lin


Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases.


BDNF Cox-2 Microglia Astrocytes Neuroinflammation 


Funding Information

This work is supported in part by grants from the Ministry of Science and Technology (102-2320-B-039-026-MY3 and 105-2320-B-039-058-), China Medical University (CMU102-ASIA-24 and CMU103-ASIA-02), Taichung Tzu Chi Hospital (TTCRD104-13 and TTCRD102-11), and Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW106-TDU-B-212-113004).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Graduate Institute of Basic Medical ScienceChina Medical UniversityTaichungTaiwan
  2. 2.Department of General Surgery, Taichung Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationTaichungTaiwan
  3. 3.School of MedicineTzu Chi UniversityHualienTaiwan
  4. 4.Department of Pharmacology, School of MedicineChina Medical UniversityTaichungTaiwan
  5. 5.Department of BiotechnologyAsia UniversityTaichungTaiwan
  6. 6.Department of BioinformaticsAsia UniversityTaichungTaiwan
  7. 7.Department of Photonics and Communication EngineeringAsia UniversityTaichungTaiwan
  8. 8.Department of Physiology, School of MedicineChina Medical UniversityTaichungTaiwan

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