Vasina Valentina, Barbara Giovanni, Talamonti Luigia, Stanghellini Vincenzo, Corinaldesi Roberto, Tonini Marcello, De Ponti Fabrizio, De Giorgio Roberto
Department of Pharmacology, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
Auton Neurosci. 2006 Jun 30;126-127:264-72. doi: 10.1016/j.autneu.2006.02.025. Epub 2006 Apr 19.
Neuroplastic changes in the enteric nervous system (ENS) may be observed in physiological states, such as development and aging, or occur as a consequence of different pathological conditions, ranging from enteric neuropathies (e.g., Hirschsprung's disease) to intestinal (e.g., inflammatory bowel disease) or extra-intestinal diseases (e.g., Parkinson's disease). Studying ENS plasticity may help to elucidate the pathophysiology of several diseases and have a bearing on the development of new pharmacological interventions. In the present review, we would like to focus on neuronal plasticity evoked by gastrointestinal inflammation occurring in inflammatory bowel disease and in a subset of patients with severe derangement of gut motility due to an enteric neuropathy characterized by an inflammatory infiltrate of the enteric plexuses. Major features of neuroplasticity within the enteric microenvironment encompass structural abnormalities ranging from nerve re-arrangement (e.g., hypertrophy and hyperplasia) to degeneration and loss of enteric ganglion cells; altered synthesis, content and release of neurotransmitters as well as up- or down-regulation of receptor systems; gastrointestinal dysfunction characterized by sensory-motor and secretory impairment of the gut. Interestingly, neuronal changes may also occur in segments of the gastrointestinal tract remote from the site of the original inflammation, e.g. the ileum may show neuroplastic changes during colitis. Sometimes, the inflamed site may even be outside the gut. Among potential mechanisms underlying ENS plasticity, neurotrophins and enteric glia deserve special attention. A better comprehension of ENS plasticity during inflammation could be instrumental to develop new therapeutic options for patients with IBD and inflammatory enteric neuropathies.
在诸如发育和衰老等生理状态下，可观察到肠神经系统（ENS）的神经可塑性变化，或者作为不同病理状况的结果而出现，这些病理状况范围从肠道神经病变（如先天性巨结肠症）到肠道疾病（如炎症性肠病）或肠外疾病（如帕金森病）。研究ENS可塑性可能有助于阐明几种疾病的病理生理学，并对新的药物干预措施的开发具有重要意义。在本综述中，我们将重点关注炎症性肠病中发生的胃肠道炎症以及因肠神经丛有炎症浸润而导致肠道运动严重紊乱的一部分患者所引发的神经元可塑性。肠微环境内神经可塑性的主要特征包括结构异常，从神经重新排列（如肥大和增生）到肠神经节细胞的变性和丧失；神经递质合成、含量和释放的改变以及受体系统的上调或下调；以肠道感觉运动和分泌功能受损为特征的胃肠功能障碍。有趣的是，神经元变化也可能发生在远离原始炎症部位的胃肠道段，例如在结肠炎期间回肠可能出现神经可塑性变化。有时，炎症部位甚至可能在肠道之外。在ENS可塑性的潜在机制中，神经营养因子和肠神经胶质值得特别关注。更好地理解炎症期间的ENS可塑性可能有助于为炎症性肠病和炎症性肠道神经病变患者开发新的治疗选择。
