Barreau Frederick, Cartier Christel, Ferrier Laurent, Fioramonti Jean, Bueno Lionel
Nuro-Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronimique, Toulouse, France.
Gastroenterology. 2004 Aug;127(2):524-34. doi: 10.1053/j.gastro.2004.05.019.
BACKGROUND & AIMS: Maternal deprivation (MD) increases nerve growth factor (NGF) expression and colonic mast cell density and alters visceral sensitivity. This study aimed to establish whether NGF overexpression induced by neonatal stress is involved in altered visceral sensitivity and gut mucosal integrity in adult rats.
Male Wistar rat pups were either submitted to MD and treated with anti-NGF antibodies or left with their dam and treated daily with NGF. All rats were tested 10 weeks later for visceral sensitivity and 12 weeks later for gut permeability, myeloperoxidase activity, and mast cell numbers. Colonic NGF and NGF receptor expression were determined at 14 days and 12 weeks of age. To determine the involvement of colonic NGF overexpression and mast cell hyperplasia in visceral hyperalgesia induced by MD, neonatally deprived adult rats received anti-NGF antibodies or doxantrazole.
MD increased visceral sensitivity to rectal distention, gut permeability, colonic myeloperoxidase activity, and mast cell density, and anti-NGF antibodies abolished these effects. Neonatal daily treatment with NGF mimicked the alterations induced by MD on both rectal sensitivity and mucosal barrier. In deprived compared with nondeprived rats, colonic NGF immunostaining and NGF messenger RNA were increased at 14 days and 12 weeks. Overexpression of NGF receptor messenger RNA, present at 14 days, was not observed later. Moreover, adult deprived rats treated with doxantrazole or anti-NGF antibodies exhibited normal gut permeability and visceral sensitivity to rectal distention.
These data indicate that NGF triggers and maintains long-term alterations of visceral sensitivity and gut mucosal integrity induced by MD.
母体剥夺（MD）会增加神经生长因子（NGF）的表达、结肠肥大细胞密度并改变内脏敏感性。本研究旨在确定新生期应激诱导的NGF过表达是否与成年大鼠内脏敏感性改变和肠道黏膜完整性有关。
雄性Wistar大鼠幼崽要么接受母体剥夺并给予抗NGF抗体治疗，要么与母鼠待在一起并每天给予NGF。10周后对所有大鼠进行内脏敏感性测试，12周后检测肠道通透性、髓过氧化物酶活性和肥大细胞数量。在14天和12周龄时测定结肠NGF和NGF受体的表达。为了确定结肠NGF过表达和肥大细胞增生在母体剥夺诱导的内脏痛觉过敏中的作用，新生期被剥夺的成年大鼠接受抗NGF抗体或多沙唑嗪治疗。
母体剥夺增加了对直肠扩张的内脏敏感性、肠道通透性、结肠髓过氧化物酶活性和肥大细胞密度，而抗NGF抗体消除了这些影响。新生期每日给予NGF模拟了母体剥夺对直肠敏感性和黏膜屏障的影响。与未被剥夺的大鼠相比，被剥夺的大鼠在14天和12周时结肠NGF免疫染色和NGF信使核糖核酸增加。14天时存在的NGF受体信使核糖核酸的过表达在后期未观察到。此外，用多沙唑嗪或抗NGF抗体治疗的成年被剥夺大鼠表现出正常的肠道通透性和对直肠扩张的内脏敏感性。
这些数据表明，NGF触发并维持了母体剥夺诱导的内脏敏感性和肠道黏膜完整性的长期改变。
