Davidowa Helga, Li Yuzhen, Plagemann Andreas
Johannes-Mueller-Institute of Physiology, Charité--University Medicine Berlin, Germany.
Neuro Endocrinol Lett. 2005 Feb;26(1):29-34.
The anorectic and catabolic action of CART is primarily mediated by the hypothalamus. The study proved the hypothesis that neurons of the hypothalamic regulatory system of body weight differentially react to CART in dependence of the nutritional state of the animal: overweight, fed or short-term fasting.
Single unit activity was extracellularly recorded in brain slices. The action of CART was studied in brains of 1. overweight adult rats previously subjected to early postnatal overfeeding in small litters (SL), compared to control litters, 2. normal rats that were deprived of food for 24 h, compared to fed rats.
Hypothalamic dorsomedial neurons of controls, but not SL rats were significantly excited by CART, ventromedial neurons of SL rats were significantly inhibited. Also neurons of hungry rats were significantly inhibited.
Controls and overweight SL as well as fed and hungry rats differed significantly in the neuronal effects of CART. The predominant effect of the peptide did neither depend on weight nor on age of animals, but on neonatal development or nutritional state.
The increase in inhibition by CART of ventromedial and dorsomedial neuronal activity could in vivo contribute to increased food intake and reduced energy expenditure of overweight SL as of hungry rats. Since leptin is able to change synaptic wiring and the expression of excitatory and inhibitory synapses already within short time, the increased expression of inhibitory responses to CART may reflect a general mechanism in adaptation of neuronal regulatory systems to the nutritional state, in fed, adult small-litter rats acquired during the postnatal critical differentiation period, thus leading to permanently altered function.
可卡因-安非他明调节转录肽（CART）的食欲抑制和分解代谢作用主要由下丘脑介导。该研究证实了以下假设：体重调节系统的下丘脑神经元对CART的反应因动物的营养状态而异，即超重、进食或短期禁食。
在脑片中细胞外记录单个神经元活动。在以下两种情况下研究了CART的作用：1. 与对照窝相比，超重成年大鼠在出生后早期于小窝中过度喂养；2. 与进食大鼠相比，正常大鼠禁食24小时。
CART可显著兴奋对照组的下丘脑背内侧神经元，但对超重成年大鼠无此作用，超重成年大鼠的腹内侧神经元被显著抑制。饥饿大鼠的神经元也被显著抑制。
对照组与超重成年大鼠以及进食与饥饿大鼠对CART的神经元效应存在显著差异。该肽的主要作用既不取决于动物的体重，也不取决于其年龄，而是取决于新生儿发育或营养状态。
在体内，CART对腹内侧和背内侧神经元活动抑制作用的增强可能导致超重成年大鼠和饥饿大鼠的食物摄入量增加和能量消耗减少。由于瘦素能够在短时间内改变突触连接以及兴奋性和抑制性突触的表达，对CART抑制反应的增强表达可能反映了神经元调节系统适应营养状态的一般机制，这在出生后关键分化期获得的成年小窝喂养大鼠中出现，从而导致功能永久改变。
