Background: Bladder-related pain symptoms in patients with bladder pain syndrome/interstitial cystitis (BPS/IC) are often accompanied by depression and memory deficits. Magnesium deficiency contributes to neuroinflammation and is associated with pain, depression, and memory deficits. Neuroinflammation is involved in the mechanical allodynia of cyclophosphamide (CYP)-induced cystitis. Magnesium-L-Threonate (L-TAMS) supplementation can attenuate neuroinflammation. This study aimed to determine whether and how L-TAMS influences mechanical allodynia and accompanying depressive symptoms and memory deficits in CYP-induced cystitis. Methods: Injection of CYP (50 mg/kg, intraperitoneally, every 3 days for 3 doses) was used to establish a rat model of BPS/IC. L-TAMS was administered in drinking water (604 mg•kg −1 •day −1). Mechanical allodynia in the lower abdomen was assessed with von Frey filaments using the up-down method. Forced swim test (FST) and sucrose preference test (SPT) were used to measure depressive-like behaviors. Novel object recognition test (NORT) was used to detect shortterm memory function. Concentrations of Mg 2+ in serum and cerebrospinal fluid (CSF) were measured by calmagite chronometry. Western blot and immunofluorescence staining measured the expression of tumor necrosis factor-α/ nuclear factor-κB (TNF-α/NF-κB), interleukin-1β (IL-1β), and N-methyl-D-aspartate receptor type 2B subunit (NR2B) of the N-methyl-D-aspartate receptor in the L6-S1 spinal dorsal horn (SDH) and hippocampus.

No abstract

Aims Central sensitization playsimportant roles in cyclophosphamide (CYP)‐induced cystitis. In addition, as a visceral pain, CYP‐induced chronic pain shares common pathophysiological mechanisms with neuropathic pain. Previous studies demonstrated that neuregulin‐1 (Nrg1)‐ErbB signaling contributes to neuropathic pain, but whether and how this signaling influences mechanical allodynia in CYP‐induced cystitis is unclear. This study aimed to determine whether and how Nrg1‐ErbB signaling modulates mechanical allodynia in a CYP‐induced cystitis rat model. Methods Systemic injection with CYP was used to establish a rat model of bladder pain syndrome/interstitial cystitis (BPS/IC). An irreversible ErbB family receptor inhibitor, PD168393, and exogenous Nrg1 were intrathecally injected to modulate Nrg1‐ErbB signaling. Mechanical allodynia in the lower abdomen was assessed with von‐Frey filaments using the up‐down method. Western blot analysis and immunofluorescence staining were used to measure the expression of Nrg1‐ErbB signaling, Iba‐1, p‐p38, and IL‐1β in the L6‐S1 spinal dorsal horn (SDH). Results We observed upregulation of Nrg1‐ErbB signaling as well as overexpression of the microglia activation markers Iba‐1 and p‐p38 and the proinflammatory factor, interleukin‐1β (IL‐1β), in the SDH of the cystitis group. Further, treatment with PD168393 attenuated mechanical allodynia in CYP‐induced cystitis and inhibited microglia activation, leading to decreased production of IL‐1β. The inhibitor PD168393 reversed the algesic effect of exogenous Nrg1 on the cystitis model. Conclusions Nrg1‐ErbB signaling may promote microglia activation, contributing to mechanical allodynia of CYP‐induced cystitis. Our study showed that modulation of Nrg1‐ErbB signaling may have therapeutic value for treating pain symptoms in BPS/IC.

Aging has been deemed the primary factor in erectile dysfunction (ED). Herein, age-related changes in the erectile response and histomorphology were detected, and the relationship between aging and ED was investigated based on gene expression levels. Thirty male Sprague–Dawley (SD) rats were randomly divided into 6 groups, and intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured. Subsequently, the corpus cavernosum (CC) was harvested and prepared for histological examinations of apoptosis, oxidative stress (OS), and fibrosis. Then, the microarray dataset (GSE10804) was analyzed to identify differentially expressed genes (DEGs) in ED progression, and hub genes were selected. In addition, aged CC smooth muscle cells (CCSMCs) were isolated to evaluate the function of the hub gene by siRNA interference, qRT–PCR, immunofluorescence staining, enzyme-linked immunosorbent assay, western blot analysis, CCK-8 assay, EdU staining, and flow cytometry approaches. The ICP/MAP and smooth muscle cell (SMC)/collagen ratios declined with aging, while apoptosis and OS levels increased with aging. The enriched functions and pathways of the DEGs were investigated, and 15 hub genes were identified, among which IGFBP3 was significantly upregulated. The IGFBP3 upregulation was verified in the CC of aging rats. Furthermore, aged CCSMCs were transfected with siRNA to knock down IGFBP3 expression. The viability and proliferation of the CCSMCs increased, while apoptosis, OS, and fibrosis decreased. Our findings demonstrate that the erectile response of SD rats declines in parallel with enhanced CC apoptosis, OS, and fibrosis with aging. Upregulation of IGFBP3 plays an important role; furthermore, downregulation of IGFBP3 improves the viability and proliferation of CCSMCs and alleviates apoptosis, OS, and fibrosis. Thus, IGFBP3 is a potential therapeutic target for age-related ED.

No abstract