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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.JN

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.

Authors+Show Affiliations

Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Rehabilitation, The Third Affiliated Hospital and Lingnan Hospital of the Sun Yat-Sen University, 2693 Kaichuang Rd, Guangzhou, 510700, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China.Pain Research Center and Department of Physiology, Zhongshan School of Medicine of Sun Yat-sen University, 74 Zhongshan Rd. 2, Guangzhou, 510080, China. Guangdong Provincial Key Laboratory of Brain Function and Disease, 74 Zhongshan Rd. 2, Guangzhou, 510080, China.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China. liubolong.happy@163.com.Department of Urology, the Third Affiliated hospital of Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, China. xiangfuzhou1962@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31931832

Citation

Ding, Honglu, et al. "BDNF Promotes Activation of Astrocytes and Microglia Contributing to Neuroinflammation and Mechanical Allodynia in Cyclophosphamide-induced Cystitis." Journal of Neuroinflammation, vol. 17, no. 1, 2020, p. 19.
Ding H, Chen J, Su M, et al. BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis. J Neuroinflammation. 2020;17(1):19.
Ding, H., Chen, J., Su, M., Lin, Z., Zhan, H., Yang, F., Li, W., Xie, J., Huang, Y., Liu, X., Liu, B., & Zhou, X. (2020). BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis. Journal of Neuroinflammation, 17(1), 19. https://doi.org/10.1186/s12974-020-1704-0
Ding H, et al. 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. PubMed PMID: 31931832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis. AU - Ding,Honglu, AU - Chen,Jialiang, AU - Su,Minzhi, AU - Lin,Zhijun, AU - Zhan,Hailun, AU - Yang,Fei, AU - Li,Wenbiao, AU - Xie,Juncong, AU - Huang,Yong, AU - Liu,Xianguo, AU - Liu,Bolong, AU - Zhou,Xiangfu, Y1 - 2020/01/13/ PY - 2019/09/05/received PY - 2020/01/07/accepted PY - 2020/1/15/entrez PY - 2020/1/15/pubmed PY - 2020/11/18/medline KW - Astrocytes KW - BDNF KW - Cystitis KW - Mechanical allodynia KW - Microglia KW - Neuroinflammation KW - TrkB SP - 19 EP - 19 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 17 IS - 1 N2 - 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/31931832/BDNF_promotes_activation_of_astrocytes_and_microglia_contributing_to_neuroinflammation_and_mechanical_allodynia_in_cyclophosphamide_induced_cystitis_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-1704-0 DB - PRIME DP - Unbound Medicine ER -