Experimental Autoimmune Prostatitis Induces Learning-Memory Impairment and Structural Neuroplastic Changes in Mice

Du, Hexi; Chen, Xianguo; Zhang, Li; Liu, Yi; Zhan, Chang-Sheng; Chen, Jing; Wang, Hui; Yu, Ziqiang; Liang, Chaozhao

doi:10.1007/s10571-019-00723-2

Cited by 18 publications

(21 citation statements)

References 33 publications

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“…In this study, we used EAP rats as subjects to explore the mechanism on the high incidence of PE in patients with prostatitis. Previous studies have shown that EAP rat is a mature animal model mimicking human CP/CPPS 8‐11,23 . However, no studies have been conducted to observe and evaluate the ejaculatory behavior of the EAP model.…”

Section: Discussionmentioning

confidence: 99%

“…These receptors and their neurotransmitters form complex networks of interactions, and our present results are probably an account of the balance of multiple effects. Currently, increasing researches have searched out various clues and regarded prostate‐derived inflammation cytokines as the key, who crossing the blood‐brain barrier to intervene the CNS 8‐11 . Therefore, developing practical clinical strategies, such as antibodies of inflammation cytokines, to eliminate or block prostate‐derived cytokines might cure or relieve PE symptom for CP/CPPS patients.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, the paraffin‐embedded tissues were cut into 5‐μm sections and stained with hematoxylin and eosin. Inflammation status of the prostate was scored according to a visual examination of perivascular cuffing with mononuclear infiltrating and vascular congestion (0 = normal, 1 = slight, 2 = moderate and 3 = intensive) 10,25 by two pathologists.…”

Section: Methodsmentioning

confidence: 99%

“…On the days −2 (baseline), 5, 20, and 35 (respective five days after each autoimmune injection) of the experimental timeline (Figure 1), the sense threshold of tactile allodynia was measured to determine the development of chronic pelvic pain using Electronic von Frey Aesthesiometer (evF, IITC Life Sciences) with rigid filaments. 10,11 When rats remained quiet in testing cages with a wire mesh bottom, stimulation was given on the lower abdominal skin by evF filaments in ascending order of force until animals had positive action responses (sudden abdomen contraction, immediate jumping, licking or scratching the simulated positions, etc). 10 The average threshold value of three stimulations was recorded for analysis.…”

Section: Tactile Allodynia Assessmentmentioning

confidence: 99%

“…[5][6][7] In recent years, there have been growing recognition on the association between CP/CPPS and central mental health disorders (MHD) including anxiety-/ depression-like symptoms, impaired spatial/ associative memory performance, and increased susceptibility to seizures. [8][9][10][11] Through the studies of experimental autoimmune prostatitis (EAP) animal models, some possible molecular mechanisms have been proposed that prostate-derived cytokines cross the blood-brain barrier to activate ERK1/2 signaling pathways in multiple regions of the brain, or microglia activation leads to changes in synaptic plasticity and neurotransmitter metabolism. [8][9][10][11] Although the exact mechanism behind the association remains obscure, the long-term adverse effects caused by CP/CPPS on central nervous system (CNS) cannot be ignored.…”

Section: Introductionmentioning

confidence: 99%

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Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis

Yang

Zhang

et al. 2020

Andrology

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Background Estimated 30%‐40% of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) suffer from premature ejaculation (PE), which is difficult to cure, but the mechanism is still unknown. Based on the results of our previous clinical studies and animal experiments, we propose that the glutamatergic system dysfunction in the paraventricular nucleus (PVN) may be involved. Methods To test this hypothesis, we used experimental autoimmune prostatitis (EAP) rats to investigate the effects of CP/CPPS on ejaculation behavior through integrating copulatory behavior testing, neuroelectrophysiologic experiments, and molecular biology technologies. Results Histological examination of prostate tissue in EAP rats exhibited consistent pathological findings with that in CP/CPPS patients. Behavior testing showed that ejaculation latency (EL) of EAP rats significantly shortened compared with the controls (5.1 ± 1.8 vs 9.1 ± 2.4 min, P < .001). Sympathetic nervous system (SNS) activity testing revealed that EAP rats displayed significantly higher plasma norepinephrine (NE) level (1780 ± 493 vs 1421 ± 453 pg/mL, P = .043) and SNS sensitivity (67.8 ± 9.6 vs 44.6 ± 8.7%, P < .001). Immunohistochemical detection and Western blot analysis both displayed that NR1 subunit expression of N‐methyl‐D‐aspartic acid (NMDA) receptors in the PVN of EAP rats was significantly upregulated (P = .007 and P < .001). Furthermore, the expression of NMDA NR1 subunit positively correlated both with SNS sensitivity (r = .917, P < .001) and prostatic inflammation scores (r = .964, P < .001). Conclusion This study shows that EAP rats suffer from the same PE symptom as CP/CPPS patients. CP/CPPS‐induced inflammatory‐immune response can significantly upregulate the expression of NMDA receptors in the PVN, which shortening the EL by enhancing SNS sensitivity. However, the exact mechanism of chronic inflammation in the prostate causing the upregulated expression of NMDA receptors needs to be further studied.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Tactile Allodynia Assessmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis

Yang

Zhang

et al. 2020

Andrology

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Molecular mechanism and promising treatments of chronic prostatitis/chronic pelvic pain syndrome: An exploratory bibliometric analysis and literature review of preclinical studies

Lao,

Guan,

Wang

et al. 2023

UroPrecision

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BackgroundAs one of the most common diseases in urology, a large number of preclinical studies have been accumulated to explore the etiological mechanism and potential intervention of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).MethodsIn this study, we systematically evaluated the current status of preclinical research on CP/CPPS through bibliometrics analysis using VOSviewer and Citespace. Characteristics of publication such as year, country/region, institution, author, journal, citation, and keywords were analyzed. Based on the bibliometrics analysis results of keywords, we summarized the possible mechanisms and promising treatments for CP/CPPS narratively.ResultsAccording to the results of this study, the most common mechanisms involved in CP/CPPS were as follows: disturbed immune and inflammation mediators, immune cell dysfunction, oxidative stress, dysregulated signaling pathways, apoptosis, gut microbiota, and testosterone metabolism. Chinese Traditional Medicine and extracorporeal shock wave therapy have important potential in the treatment of CP/CPPS.ConclusionFurther translational studies targeting the above mechanisms and validating the objective efficacy of potential treatments indicated by preclinical studies in clinical patients are needed in the future.

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Determining factors for optimal neuronal and glial Golgi-Cox staining

Narayanan

Bairy

Srinivasamurthy

2020

Histochem Cell Biol

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Experimental Autoimmune Prostatitis Induces Learning-Memory Impairment and Structural Neuroplastic Changes in Mice

Cited by 18 publications

References 33 publications

Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis

Upregulated expression of NMDA receptor in the paraventricular nucleus shortens ejaculation latency in rats with experimental autoimmune prostatitis

Molecular mechanism and promising treatments of chronic prostatitis/chronic pelvic pain syndrome: An exploratory bibliometric analysis and literature review of preclinical studies

Determining factors for optimal neuronal and glial Golgi-Cox staining

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