THE IMMUNOLOGICAL IMPAIRMENT OF ARCUATE NEUROPEPTIDE-Y NEURONS BY RICIN-A CHAIN PRODUCES PERSISTENT DECREASE OF FOOD-INTAKE AND BODY-WEIGHT
THE IMMUNOLOGICAL IMPAIRMENT OF ARCUATE NEUROPEPTIDE-Y NEURONS BY RICIN-A CHAIN PRODUCES PERSISTENT DECREASE OF FOOD-INTAKE AND BODY-WEIGHT
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DOI：
10.1016/0306-4522(94)00573-n
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发表时间：
1995-05-01
期刊：
影响因子：
3.3
通讯作者：
BURLET, C
中科院分区：
文献类型：
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作者：
BURLET, A;GROUZMANN, E;BURLET, C
神经肽Y被证明是一种有效的食欲肽时，注射到大鼠下丘脑室旁核。室旁核的神经肽Y神经支配来源于下丘脑弓状核和脑干神经元，其在摄食控制中的具体作用仍在讨论中。为了评估弓状神经肽Y在调节食物摄入中的作用，我们提出了一种新的方法，从一个独特的大脑部位免疫损伤神经肽Y的神经元分泌。神经肽Y前体表位的单克隆抗体，C-侧翼肽，与两种细胞毒素（蓖麻毒素A链和莫能菌素）显微注射到下丘脑弓状核或室旁核。弓状核内微量注射一次可减少摄食量和体重增加，持续10天。它阻止了通常由12小时食物剥夺引起的食物摄入刺激。这种摄食量的减少不是由于单克隆抗体或细胞毒素的厌恶性质，或生物活性神经肽Y的免疫中和作用，因为（i）向弓状核中微量注射的急性效应促进了摄食量的短暂增加，这可能是由免疫损伤的弓状神经元强烈释放神经肽Y引起的，和（ii）C-侧翼肽单克隆抗体既不结合神经肽Y也不结合其受体。当用非特异性大鼠免疫球蛋白替代C-侧翼肽单克隆抗体或将C-侧翼肽单克隆抗体/毒素混合物注射到室旁核时，显微注射效率低下。在摄食调节中，我们的数据证实了下丘脑弓状核在向室旁核提供神经肽Y传入中的主要作用。另一方面，细胞毒素可以用不能与生物活性肽相互作用的抗体免疫地引入肽能神经元。这为抑制中枢神经肽的分泌提供了新的途径。
Neuropeptide Y is demonstrated as a potent orexigenic peptide when injected into the rat hypothalamic paraventricular nuclei. The neuropeptide Y innervation of paraventricular nuclei originates from both hypothalamic arcuate nuclei and brainstem neurons, whose specific role in the control of food intake is still under discussion. To assess the role of the arcuate neuropeptide Y in the regulation of food intake, we propose a new method for immunologically impairing the neuronal secretion of neuropeptide Y from a unique brain site.The monoclonal antibody to the neuropeptide Y precursor epitope, the C-flanking peptide, was microinjected with two cellular toxins (the ricin A chain and the monensin) into the hypothalamic arcuate nuclei or paraventricular nuclei. One microinjection into the arcuate nuclei reduced the food intake and body weight gain for 10 days. It prevented the food intake stimulation usually induced by a 12 h food deprivation. This decrease of food intake was not due to the aversive properties of monoclonal antibody or cellular toxins, or the immunoneutralization of the biologically active neuropeptide Y, because (i) the acute effect of the microinjection into the arcuate nuclei promoted a transient increase of the food intake likely induced by a strong release of neuropeptide Y from the arcuate neurons which were immunologically damaged, and (ii) the C-flanking peptide monoclonal antibody binds neither neuropeptide Y nor its receptors. The microinjection was inefficient when C-flanking peptide monoclonal antibody was replaced by non-specific rat immunoglobulins or when the C-flanking peptide monoclonal antibody/toxins mixture was injected into the paraventricular nuclei.The data bring further arguments in two domains. In the food intake regulation, our data confirm the major role of the hypothalamic arcuate nuclei in providing neuropeptide Y afferents to the paraventricular nuclei. On the other hand, cellular toxins can be immunologically introduced into peptidergic neurons with an antibody unable to interact with biologically active peptide. This offers a new approach to inhibiting the secretion of a central neuropeptide.