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Bladder outlet obstruction influences mRNA expression of cholinergic receptors on sensory neurons in mice.

机译:膀胱出口梗阻影响小鼠感觉神经元中胆碱能受体的mRNA表达。

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In patients with bladder outlet obstruction (BOO), dysregulation of bladder afferent neurons seems to contribute to irritative symptoms. Cholinergic receptors, addressed by both neuronal and non-neuronal (urothelial) acetylcholine, can alter neuronal excitability. Thus we investigated the influence of BOO on the expression of muscarinic (mAChR) and nicotinic (nAChR) acetylcholine receptors in the lumbosacral dorsal root ganglia (DRG) of mice.BOO was induced in 13 C57/BL6 mice by partial suturing of the urethra. Eleven mice were sham-operated (loose/freely movable suture around the urethra), and eleven untreated mice served as controls. Cystometry was performed five weeks later in conscious mice. DRG at segmental levels L5-S2 were dissected and real-time quantitative PCR was performed. Expression of mAChR subtypes M1-M5 and nAChR subunits α2-7, α9-10, β2-4 was examined.Expression of all mAChR subtypes and nAChR subunits α3-7, α10, β2-4 was detected. Expression of α2 and α9 was absent. Rank order of expression was M2>M4>M3>M5>M1, α3≥α6>α7>α4>α10>α5 and β2>β4>β3 in untreated animals. BOO mice presented distinct obstruction with development of residual urine. Sham mice showed only minimal BOO. Relative mRNA expression of nAChR subunits revealed significant reduction of α3, α5, α6, α10 and β4 in sham-operated vs. untreated mice. In BOO vs. sham-operated mice, reduction of nAChR subunits α10 (p=0.038) and α5 (p=0.053) was found.BOO has a considerable impact on nAChR, but not on mAChR mRNA expression in sensory neurons. We hypothesize that a reduction in mRNA expression of nAChR subunits represents a link to altered sensitivity under non-obstructive conditions.
机译:在患有膀胱出口梗阻(BOO)的患者中,膀胱传入神经元的失调似乎是刺激性症状的原因。由神经元和非神经元(尿路上皮)乙酰胆碱处理的胆碱能受体可以改变神经元的兴奋性。因此,我们研究了BOO对小鼠腰s背根神经节(DRG)中毒蕈碱(mAChR)和烟碱(nAChR)乙酰胆碱受体表达的影响。通过部分缝合尿道在13例C57 / BL6小鼠中诱导了BOO。假手术11只小鼠(尿道周围的松散/可自由移动的缝合线),而11只未治疗的小鼠用作对照。五周后在有意识的小鼠中进行膀胱测量。解剖在节段水平L5-S2的DRG,并进行实时定量PCR。检测mAChR亚型M1-M5和nAChR亚基α2-7,α9-10,β2-4的表达。检测所有mAChR亚型和nAChR亚基α3-7,α10,β2-4的表达。 α2和α9的表达不存在。在未经处理的动物中,表达的排名顺序为M2> M4> M3> M5> M1,α3≥α6>α7>α4>α10>α5和β2>β4>β3。 BOO小鼠表现出明显的梗阻,并伴有残留尿液的发展。假鼠只表现出最小的BOO。与未经治疗的假手术组相比,nAChR亚基的相对mRNA表达显示出α3,α5,α6,α10和β4的显着降低。在BOO与假手术小鼠中,发现nAChR亚基α10(p = 0.038)和α5(p = 0.053)减少.BOO对nAChR有很大影响,但对感觉神经元中的mAChR mRNA表达没有影响。我们假设nAChR亚基的mRNA表达的减少代表在非阻塞性条件下敏感性改变的链接。

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