EA 4674, Laboratoire de Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif, FST St Jérôme. Aix-Marseille Université, Avenue Escadrille Normandie-Niemen, 13013 Marseille, France.
EA 4674, Laboratoire de Physiologie et Physiopathologie du Système Nerveux Somato-Moteur et Neurovégétatif, FST St Jérôme. Aix-Marseille Université, Avenue Escadrille Normandie-Niemen, 13013 Marseille, France; INRA U1189, Département AlimH, 63122 St Genés Champenelle, France.
Brain Behav Immun. 2014 Mar;37:54-72. doi: 10.1016/j.bbi.2013.12.008. Epub 2013 Dec 16.
T-2 toxin is one of the most toxic Fusarium-derived trichothecenes found on cereals and constitutes a widespread contaminant of agricultural commodities as well as commercial foods. Low doses toxicity is characterized by reduced weight gain. To date, the mechanisms by which this mycotoxin profoundly modifies feeding behavior remain poorly understood and more broadly the effects of T-2 toxin on the central nervous system (CNS) have received limited attention. Through an extensive characterization of sickness-like behavior induced by T-2 toxin, we showed that its per os (p.o.) administration affects not only feeding behavior but also energy expenditure, glycaemia, body temperature and locomotor activity. Using c-Fos expression mapping, we identified the neuronal structures activated in response to T-2 toxin and observed that the pattern of neuronal populations activated by this toxin resembled that induced by inflammatory signals. Interestingly, part of neuronal pathways activated by the toxin were NUCB-2/nesfatin-1 expressing neurons. Unexpectedly, while T-2 toxin induced a strong peripheral inflammation, the brain exhibited limited inflammatory response at a time point when anorexia was ongoing. Unilateral vagotomy partly reduced T-2 toxin-induced brainstem neuronal activation. On the other hand, intracerebroventricular (icv) T-2 toxin injection resulted in a rapid (<1h) reduction in food intake. Thus, we hypothesized that T-2 toxin could signal to the brain through neuronal and/or humoral pathways. The present work provides the first demonstration that T-2 toxin modifies feeding behavior by interfering with central neuronal networks devoted to central energy balance. Our results, with a particular attention to peripheral inflammation, strongly suggest that inflammatory mediators partake in the T-2 toxin-induced anorexia and other symptoms. In view of the broad human and breeding animal exposure to T-2 toxin, this new mechanism may lead to reconsider the impact of the consumption of this toxin on human health.
T-2 毒素是谷物中发现的最具毒性的伏马菌素之一，也是农业商品和商业食品中广泛存在的污染物。低剂量毒性的特征是体重增加减少。迄今为止，这种霉菌毒素如何深刻改变摄食行为的机制仍知之甚少，更广泛地说，T-2 毒素对中枢神经系统（CNS）的影响受到的关注有限。通过对 T-2 毒素引起的类似疾病行为进行广泛表征，我们表明其口服（p.o.）给药不仅影响摄食行为，还影响能量消耗、血糖、体温和运动活动。使用 c-Fos 表达图谱，我们确定了 T-2 毒素激活的神经元结构，并观察到该毒素激活的神经元群体模式类似于炎症信号诱导的模式。有趣的是，部分被毒素激活的神经元途径是 NUCB-2/nesfatin-1 表达神经元。出乎意料的是，虽然 T-2 毒素引起强烈的外周炎症，但当厌食症持续存在时，大脑显示出有限的炎症反应。单侧迷走神经切断术部分减少了 T-2 毒素诱导的脑干神经元激活。另一方面，脑室（icv）内注射 T-2 毒素会导致食物摄入迅速（<1h）减少。因此，我们假设 T-2 毒素可以通过神经元和/或体液途径向大脑发出信号。本工作首次证明 T-2 毒素通过干扰中枢神经元网络来改变摄食行为，该网络专门用于中枢能量平衡。我们的结果，特别是对外周炎症的关注，强烈表明炎症介质参与了 T-2 毒素引起的厌食症和其他症状。鉴于人类和繁殖动物广泛接触 T-2 毒素，这种新机制可能会促使重新考虑摄入这种毒素对人类健康的影响。
