Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis.

Jie Yang; Jiao-chen Luan; Jian-huai Chen; Qi-jie Zhang; Jian-xin Xue; Ya-min Wang; Guo-qing Zhu; Ning-hong Song; Zeng-jun Wang; Jia-dong Xia

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Prostate-derived IL-1β upregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis.

Author: Jie YANG ¹ ; Jiao-Chen LUAN ¹ ; Jian-Huai CHEN ² ; Qi-Jie ZHANG ¹ ; Jian-Xin XUE ¹ ; Ya-Min WANG ¹ ; Guo-Qing ZHU ³ ; Ning-Hong SONG ¹ ; Zeng-Jun WANG ¹ ; Jia-Dong XIA ¹
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1. Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210008, China.
2. Department of Andrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210008, China.
3. Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210008, China.
Publication Type:Journal Article
Keywords: N-methyl-D-aspartic acid receptor; chronic prostatitis; paraventricular nucleus; premature ejaculation; prostate-derived inflammation cytokines; sympathetic nervous system
MeSH: Animals; Cytokines/metabolism*; Disease Models, Animal; Ejaculation/physiology*; Interleukin-1beta/metabolism*; Male; N-Methylaspartate/metabolism*; Prostate/metabolism*; Prostatitis/metabolism*; Rats; Receptors, N-Methyl-D-Aspartate/metabolism*
From: Asian Journal of Andrology 2022;24(2):213-218
CountryChina
Language:English
Abstract: Experimental autoimmune prostatitis (EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid (NMDA) receptors in the paraventricular nucleus (PVN). However, the mechanism has not yet been elucidated. Herein, we screened out the target prostate-derived inflammation cytokines (PDICs) by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid (CSF) between EAP rats and their controls. After identifying the target PDIC, qualified males in initial copulatory behavior testing (CBT) were subjected to implanting tubes onto bilateral PVN. Next, they were randomly divided into four subgroups (EAP-1, EAP-2, Control-1, and Control-2). After 1-week recovery, EAP-1 rats were microinjected with the target PDIC inhibitor, Control-1 rats were microinjected with the target PDIC, while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF (aCSF). Results showed that only interleukin-1β(IL-1β) had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls (P < 0.001) and significantly higher protein concentrations in both the serum (P = 0.001) and CSF (P < 0.001) of the EAP groups compared to the Control groups. Therefore, IL-1β was identified as the target PDIC which crosses the blood-brain barrier, thereby influencing the central nervous system. Moreover, the EAP-1 subgroup displayed a gradually prolonged ejaculation latency (EL) in the last three CBTs (all P < 0.01) and a significantly lower expression of NMDA NR1 subunit in the PVN (P = 0.043) compared to the respective control groups after a 10-day central administration of IL-1β inhibitors. However, the Control-1 subgroup showed a gradually shortened EL (P < 0.01) and a significantly higher NR1 expression (P = 0.004) after homochronous IL-1β administration. Therefore, we identified IL-1β as the primary PDIC which shortens EL in EAP rats. However, further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1β upregulates NMDA expression.