Bossowska Agnieszka, Lepiarczyk Ewa, Mazur Urszula, Janikiewicz Paweł, Markiewicz Włodzimierz
Department of Human Physiology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Warszawska 30, Olsztyn 10-082, Poland.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, Olsztyn 10-719, Poland.
Toxins (Basel). 2015 Nov 16;7(11):4797-816. doi: 10.3390/toxins7114797.
Botulinum toxin (BTX) is a potent neurotoxin which blocks acetylcholine release from nerve terminals, and therefore leads to cessation of somatic motor and/or parasympathetic transmission. Recently it has been found that BTX also interferes with sensory transmission, thus, the present study was aimed at investigating the neurochemical characterization of substance P-immunoreactive (SP-IR) bladder-projecting sensory neurons (BPSN) after the toxin treatment. Investigated neurons were visualized with retrograde tracing method and their chemical profile was disclosed with double-labelling immunohistochemistry using antibodies against SP, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP), neuronal nitric oxide synthase (nNOS), galanin (GAL), calbindin (CB), and somatostatin (SOM). In the control group (n = 6), 45% of the total population of BPSN were SP-IR. Nearly half of these neurons co-expressed PACAP or CGRP (45% and 35%, respectively), while co-localization of SP with GAL, nNOS, SOM or CB was found less frequently (3.7%, 1.8%, 1.2%, and 0.7%, respectively). In BTX-treated pigs (n = 6), toxin-injections caused a decrease in the number of SP-IR cells containing CGRP, SOM or CB (16.2%, 0.5%, and 0%, respectively) and a distinct increase in these nerve cells immunopositive to GAL (27.2%). The present study demonstrates that BTX significantly modifies the chemical phenotypes of SP-IR BPSN.
肉毒杆菌毒素(BTX)是一种强效神经毒素,它会阻断神经末梢释放乙酰胆碱,从而导致躯体运动和/或副交感神经传递停止。最近发现,BTX还会干扰感觉传递,因此,本研究旨在调查毒素处理后P物质免疫反应性(SP-IR)膀胱投射感觉神经元(BPSN)的神经化学特征。使用逆行追踪法对所研究的神经元进行可视化,并通过双重标记免疫组织化学法揭示其化学特征,所用抗体针对P物质、降钙素基因相关肽(CGRP)、垂体腺苷酸环化酶激活多肽(PACAP)、神经元型一氧化氮合酶(nNOS)、甘丙肽(GAL)、钙结合蛋白(CB)和生长抑素(SOM)。在对照组(n = 6)中,BPSN总数的45%为SP-IR。这些神经元中近一半共表达PACAP或CGRP(分别为45%和35%),而SP与GAL、nNOS、SOM或CB的共定位较少见(分别为3.7%、1.8%、1.2%和0.7%)。在接受BTX治疗的猪(n = 6)中,注射毒素导致含有CGRP、SOM或CB的SP-IR细胞数量减少(分别为16.2%、0.5%和0%),而对GAL呈免疫阳性的这些神经细胞数量明显增加(27.2%)。本研究表明,BTX可显著改变SP-IR BPSN的化学表型。