2. Academic Validation
  3. BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis

  • J Neuroinflammation. 2020 Jan 13;17(1):19. doi: 10.1186/s12974-020-1704-0.
Honglu Ding 1,  Jialiang Chen 1,  Minzhi Su 2,  Zhijun Lin 1,  Hailun Zhan 1,  Fei Yang 1,  Wenbiao Li 1,  Juncong Xie 1,  Yong Huang 1,  Xianguo Liu 3 4,  Bolong Liu 5,  Xiangfu Zhou 6
Affiliations

Affiliations

  • 1 Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.
  • 2 Department of Rehabilitation, The Third Affiliated Hospital and Lingnan Hospital of the Sun Yat-Sen University, 2693 Kaichuang Rd, Guangzhou, 510700, China.
  • 3 Pain Research Center and Department of Physiology, Zhongshan School of Medicine of Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou, 510080, China.
  • 4 Guangdong Provincial Key Laboratory of Brain Function and Disease, 74 Zhongshan Rd. 2, Guangzhou, 510080, China.
  • 5 Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China. [email protected].
  • 6 Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China. [email protected].
PMID: 31931832 DOI: 10.1186/s12974-020-1704-0
Abstract

Background: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) often grieve over a low quality of life brought about by chronic pain. In our previous studies, we determined that neuroinflammation of the spinal dorsal horn (SDH) was associated with mechanisms of interstitial cystitis. Moreover, it has been shown that brain-derived neurotrophic factor (BDNF) participates in the regulation of neuroinflammation and pathological pain through BDNF-TrkB signaling; however, whether it plays a role in cyclophosphamide (CYP)-induced cystitis remains unclear. This study aimed to confirm whether BDNF-TrkB signaling modulates neuroinflammation and mechanical allodynia in CYP-induced cystitis and determine how it occurs.

Methods: Systemic intraperitoneal injection of CYP was performed to establish a rat cystitis model. BDNF-TrkB signaling was modulated by intraperitoneal injection of the TrkB receptor antagonist, ANA-12, or intrathecal injection of exogenous BDNF. Mechanical allodynia in the suprapubic region was assessed using the von Frey filaments test. The expression of BDNF, TrkB, p-TrkB, Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the L6-S1 SDH was measured by Western blotting and immunofluorescence analysis.

Results: BDNF-TrkB signaling was upregulated significantly in the SDH after CYP was injected. Similarly, the expressions of Iba1, GFAP, p-p38, p-JNK, IL-1β, and TNF-α in the SDH were all upregulated. Treatment with ANA-12 could attenuate mechanical allodynia, restrain activation of astrocytes and microglia and alleviate neuroinflammation. Besides, the intrathecal injection of exogenous BDNF further decreased the mechanical withdrawal threshold, promoted activation of astrocytes and microglia, and increased the release of TNF-α and IL-1β in the SDH of our CYP-induced cystitis model.

Conclusions: In our CYP-induced cystitis model, BDNF promoted the activation of astrocytes and microglia to release TNF-α and IL-1β, aggravating neuroinflammation and leading to mechanical allodynia through BDNF-TrkB-p38/JNK signaling.

Keywords

Astrocytes; BDNF; Cystitis; Mechanical allodynia; Microglia; Neuroinflammation; TrkB.

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