Lepiarczyk E, Bossowska A, Majewski M
Department of Human Physiology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Warszawska 30, 10-082, Olsztyn, Poland,
Cell Tissue Res. 2015 May;360(2):263-72. doi: 10.1007/s00441-014-2086-3. Epub 2015 Jan 27.
Botulinum toxin (BTX) is a neurotoxin used in medicine as an effective drug in experimental therapy of neurogenic urinary bladder disorders. We have investigated the influence of BTX on the chemical coding of sympathetic chain ganglia (SChG) neurons supplying the porcine urinary bladder. The toxin was injected into the wall of the bladder. SChG neurons were visualized by a retrograde tracing method with fluorescent tracer fast blue (FB) and their chemical coding was investigated by double-labelling immunohistochemistry with antibodies against dopamine β-hydroxylase (DβH; a marker of noradrenergic neurons), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin (GAL), Leu(5)-enkephalin (L-ENK) and neuronal nitric oxide synthase (nNOS). In both the control (n = 5) and BTX-treated pigs (n = 5), the vast majority (91 ± 2.3 % and 89.8 ± 2.5 %, respectively) of FB-positive (FB+) nerve cells were DβH+. BTX injections caused a decrease in the number of FB+/DβH+ neurons that were immunopositive to NPY (39.5 ± 4.5 % vs 74.5 ± 11.9 %), VIP (8.9 ± 5.3 % vs 22.3 ± 8.8 %), SOM (5.8 ± 2.3 % vs 17.4 ± 3.7 %) or GAL (0.9 ± 1.2 % vs 5.4 ± 4.4 %) and a distinct increase in the number of FB+/DβH+ neurons that were immunoreactive to L-ENK (3.7 ± 2.9 % vs 1.1 % ± 0.8 %) or nNOS (7.7 ± 3.5 % vs 0.8 ± 0.6 %). Our study provides novel evidence that the therapeutic effects of BTX on the mammalian urinary bladder are partly mediated by SChG neurons.
肉毒杆菌毒素（BTX）是一种神经毒素，在医学上用作治疗神经源性膀胱疾病的有效实验性药物。我们研究了BTX对支配猪膀胱的交感神经链神经节（SChG）神经元化学编码的影响。将毒素注入膀胱壁。通过逆行示踪法用荧光示踪剂快蓝（FB）使SChG神经元可视化，并通过用抗多巴胺β-羟化酶（DβH；去甲肾上腺素能神经元的标志物）、神经肽Y（NPY）、血管活性肠多肽（VIP）、生长抑素（SOM）、甘丙肽（GAL）、亮氨酸脑啡肽（L-ENK）和神经元型一氧化氮合酶（nNOS）的抗体进行双重标记免疫组织化学来研究其化学编码。在对照猪（n = 5）和经BTX处理的猪（n = 5）中，绝大多数（分别为91±2.3%和89.8±2.5%）的FB阳性（FB+）神经细胞为DβH+。注射BTX导致对NPY免疫阳性的FB+/DβH+神经元数量减少（39.5±4.5%对74.5±11.9%）、对VIP免疫阳性的FB+/DβH+神经元数量减少（8.9±5.3%对22.3±8.8%）、对SOM免疫阳性的FB+/DβH+神经元数量减少（5.8±2.3%对17.4±3.7%）或对GAL免疫阳性的FB+/DβH+神经元数量减少（0.9±1.2%对5.4±4.4%），而对L-ENK免疫反应阳性的FB+/DβH+神经元数量明显增加（3.7±2.9%对1.1%±0.8%）或对nNOS免疫反应阳性的FB+/DβH+神经元数量明显增加（7.7±3.5%对0.8±0.6%）。我们的研究提供了新的证据，表明BTX对哺乳动物膀胱的治疗作用部分是由SChG神经元介导的。
