<p>Microglial activation and neurobiological alterations in experimental autoimmune prostatitis-induced depressive-like behavior in mice</p>

Abstract

Background Patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) frequently show depressive symptoms clinically and increasing evidence indicates a correlation between CP/CPPS and depression. However, the underlying mechanisms of CP/CPPS-related depression remain poorly understood. Here, we sought to determine the role of hippocampal microglial activation and neurobiological changes in a mouse model of experimental autoimmune prostatitis (EAP)-induced depression and the treatment efficacy of Chinese herb extract baicalein. Methods EAP was induced through intradermal injection of prostate antigen and adjuvant twice. Then, mice were assessed for affective behaviors in the open field test, elevated plus maze, forced swim test, and tail suspension test. The morphology and function of microglia and astrocytes were detected by immunofluorescence, Western blotting, and transmission electron microscopy. Proinflammatory mediators along with serotonin transporter (SLC6A4/SERT) and indoleamine 2,3-dioxygenase (IDO) were quantified with reverse transcription-polymerase chain reaction (RT‑PCR), and serum serotonin concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Proton magnetic resonance spectroscopy ( 1 H-MRS) was performed to measure hippocampal glutamate levels. In addition, baicalein was used in a subset of EAP mice to test its anti-depressant action. Results EAP was successfully established and induced depressive- and anxiety-like behavior in mice. Increasing levels of co-expressed ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) and ultrastructural observations suggested microglial activation and reactive astrocytosis in the hippocampus. These activated microglia resulted in increased expressions of multiple proinflammatory cytokines. Simultaneously, EAP mice showed higher gene expressions of SLC6A4 and IDO and lower concentrations of serotonin. 1 H-MRS indicated a decrease in the glutamate + glutamine (Glx)/total creatine (tCr) ratio in EAP mice. Furthermore, baicalein treatment alleviated the depressive-like behavior and neuroinflammation by suppressing the nuclear factor-kappa B (NF-κB) pathway. Conclusion Our data indicate that EAP-induced depressive-like behavior is linked to microglia activation and subsequent neurotransmitter metabolism. Moreover, baicalein attenuates behavioral changes by inhibiting neuroinflammation via downregulation of the NF-κB pathway.

Influence of Experimental Autoimmune Prostatitis on Sexual Function and the Anti-inflammatory Efficacy of Celecoxib in a Rat Model

“…The high risk of depression associated with CP/CPPS was confirmed in a clinical study and in EAP mice (6,31). The depressive state of animals is mainly manifested by a decrease in overall activity, reduced social communication activities, reduced exploratory activities, and defects in aggression and pleasure sensation (23,32).…”

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

“…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.…”

“…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.…”

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

“…However, whether gut microbiota involves in EAP‐induced depressive‐like behaviors in mice remains undetermined. Our previous work showed that emotional abnormity in EAP mice was related to microglial activation and subsequent neurobiological alterations in the brain 38 . Also, the gut microbiota has been reported to play a vital role in regulating microglial function via the gut‐brain axis 39 .…”