Johansen Jeanette E, Fetissov Sergueï, Fischer Heléne, Arvidsson Sivonne, Hökfelt Tomas, Schalling Martin
Neurogenetics Unit, Department of Molecular Medicine, L8:00, Karolinska Hospital, Karolinska Institutet, 171 76, Stockholm, Sweden.
Eur J Pharmacol. 2003 Nov 7;480(1-3):171-6. doi: 10.1016/j.ejphar.2003.08.104.
Eating disorders constitute major medical health problems in the western world. Even though little is known about the mechanisms behind abnormal eating behavior, it has become clear that the central nervous system (CNS), particularly the hypothalamus, plays a significant role. The anorexic anx/anx mouse is a unique model for studying food intake and energy expenditure. The anx mutation is linked to marked alterations in hypothalamic distributions of signal substances known to have potent regulatory roles in the control of food intake. We have identified a mutation in anx/anx mice that is likely to cause the anorectic phenotype. Using RNA profiling, we have found 29 genes with differential expression in the anx/anx mouse brain. The anx gene, its protein product or molecules in the anx pathway may thus be interesting targets for development of new pharmaceuticals for the treatment of eating disorders. Based on the histochemical alterations found in the anx/anx mouse, we hypothesised and showed that many sera from anorectic/bulimic patients contain antibodies that bind specifically to the hypothalamic food intake regulatory system in rat. This finding represents a novel research avenue that may lead to a better understanding of eating disorders. It also suggests that targeted immunological approaches may be used in therapy.
饮食失调是西方世界主要的医学健康问题。尽管对异常饮食行为背后的机制了解甚少，但已明确中枢神经系统（CNS），尤其是下丘脑，起着重要作用。厌食性anx/anx小鼠是研究食物摄入和能量消耗的独特模型。anx突变与已知在食物摄入控制中具有强大调节作用的信号物质在下丘脑分布的显著改变有关。我们在anx/anx小鼠中鉴定出一种可能导致厌食表型的突变。通过RNA谱分析，我们在anx/anx小鼠大脑中发现了29个差异表达的基因。因此，anx基因、其蛋白质产物或anx途径中的分子可能是开发治疗饮食失调新药物的有趣靶点。基于在anx/anx小鼠中发现的组织化学改变，我们进行了假设并证明，许多厌食/贪食症患者的血清中含有能与大鼠下丘脑食物摄入调节系统特异性结合的抗体。这一发现代表了一条新的研究途径，可能有助于更好地理解饮食失调。它还表明靶向免疫方法可用于治疗。
