Upregulation of spinal ASIC1 by miR‐485 mediates enterodynia in adult offspring rats with prenatal maternal stress

Abstract

Aims Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease characterized by abdominal pain. Our recent study has shown that the acid‐sensitive ion channel 1 (ASIC1) in dorsal root ganglion (DRG) is involved in stomachache of adult offspring rats subjected with prenatal maternal stress (PMS). MiR‐485 is predicted to target the expression of ASIC1. The aim of the present study was designed to determine whether miR‐485/ASIC1 signaling participates in enterodynia in the spinal dorsal horn of adult offspring rats with PMS. Methods Enterodynia was measured by colorectal distension (CRD). Western blotting, qPCR, and in situ hybridization were performed to detect the expression of ASICs and related miRNAs. Spinal synaptic transmission was also recorded by patch clamping. Results PMS offspring rats showed that spinal ASIC1 protein expression and synaptic transmission were significantly enhanced. Administration of ASICs antagonist amiloride suppressed the synaptic transmission and enterodynia. Besides, PMS induced a significant reduction in the expression of miR‐485. Upregulating the expression markedly attenuated enterodynia, reversed the increase in ASIC1 protein and synaptic transmission. Furthermore, ASIC1 and miR‐485 were co‐expressed in NeuN‐positive spinal dorsal horn neurons. Conclusions Overall, these data suggested that miR‐485 participated in enterodynia in PMS offspring, which is likely mediated by the enhanced ASIC1 activities.

Overexpression of GRK6 alleviates chronic visceral hypersensitivity through downregulation of P2Y6 receptors in anterior cingulate cortex of rats with prenatal maternal stress

“…Consistent with previous studies, 4,5,30 chronic visceral hypersensitivity was successfully induced in PMS offspring rats that were 6, 8 and 10 weeks of age, but no difference was observed in 4‐week‐old PMS rats when compared with CON rats (Figure 1B , n = 6 rats for each group, compared with CON group, ** p < 0.01, *** p < 0.001, Tukey's post hoc test following two‐way ANOVA). The expression of GRK6 mRNA in ACC of 6‐week‐old PMS rats was detected by qPCR.…”

“…Studies have reported that VH is a stress-sensitive disorder of brain-gut interactions associated with a higher prevalence of adverse early life-forming events. 3 We have previously reported that offspring rats with prenatal maternal stress (PMS) were afflicted with IBS-like visceral pain, 4,5 but the central mechanism of visceral hypersensitivity (VH) in PMS rats remains largely unclear.…”

Risk factors for irritable bowel syndrome: A review

“…Интересными представляются данные о том, что на риск возникновения СРК может влиять и психоэмоциональное состояние матери в период беременности [44]. В эксперименте пренатальный материнский стресс приводил к висцеральной гиперчувствительности и абдоминальной боли у потомства опосредованно путем повышения экспрессии цистатионин-β-синтазы и нейротрофического фактора в спинном мозге [45], а также за счет усиления передачи болевых сигналов в дорсальном роге спинного мозга в результате снижения экспрессии miR-485 и увеличения количества кислоточувствительных ионных каналов ASIC1 [46]. В клиническом исследовании J. Galley и соавт.…”

Early life adverse exposures in irritable bowel syndrome: new insights and opportunities

“…Furthermore, a rat study has shown that prenatal maternal stress can lead to visceral hypersensitivity in the offspring, and this change may be mediated by the upregulation of cystathionine-β-synthase and Nav1.7 expression. Animal studies have also reported that miR-485/ASIC1 signaling and BDNF expression are associated with the occurrence of visceral hypersensitivity in offspring following prenatal stress ( 60 , 61 ). Therefore, stress during pregnancy could also increase the risk of offspring developing IBS through a mechanism of visceral hypersensitivity ( 62 ).…”