Biology Department, Washington and Lee University, Lexington, VA, USA.
Physiol Behav. 2011 Jun 1;103(3-4):268-78. doi: 10.1016/j.physbeh.2011.02.035. Epub 2011 Mar 6.
We investigated whether histaminergic tone contributes to the seasonal catabolic state in Siberian hamsters by determining the effect of ablation of histaminergic neurons on food intake, metabolic rate and body weight. A ribosomal toxin (saporin) conjugated to orexin-B was infused into the ventral tuberomammillary region of the hypothalamus, since most histaminergic neurons express orexin receptors. This caused not only 75-80% loss of histaminergic neurons in the posterior hypothalamus, but also some loss of other orexin-receptor expressing cells e.g. MCH neurons. In the long-day anabolic state, lesions produced a transient post-surgical decrease in body weight, but the hamsters recovered and maintained constant body weight, whereas weight gradually increased in sham-lesioned hamsters. VO(2) in the dark phase was significantly higher in the lesioned hamsters compared to shams, and locomotor activity also tended to be higher. In a second study in short days, sham-treated hamsters showed the expected seasonal decrease in body weight, but weight remained constant in the lesioned hamsters, as in the long-day study. Lesioned hamsters consumed more during the early dark phase and less during the light phase due to an increase in the frequency of meals during the dark and decreased meal size during the light, and their cumulative food intake in their home cages was greater than in the control hamsters. In summary, ablation of orexin-responsive cells in the posterior hypothalamus blocks the short-day induced decline in body weight by preventing seasonal hypophagia, evidence consistent with the hypothesis that central histaminergic mechanisms contribute to long-term regulation of body weight.
我们通过确定组胺能神经元消融对食物摄入、代谢率和体重的影响，来研究组胺能张力是否有助于西伯利亚仓鼠的季节性分解代谢状态。一种核糖体毒素（蓖麻毒素）与食欲素-B 连接后被注入下丘脑腹侧结节乳头体区域，因为大多数组胺能神经元表达食欲素受体。这不仅导致下丘脑后部 75-80%的组胺能神经元丧失，而且还导致其他表达食欲素受体的细胞（例如 MCH 神经元）丧失。在长日照合成代谢状态下，损伤会导致术后体重短暂下降，但仓鼠会恢复并保持体重恒定，而假损伤仓鼠的体重逐渐增加。与假损伤组相比，损伤组在暗期的 VO2 显著升高，而运动活性也有升高趋势。在短日照的第二项研究中，与假处理组相比，接受假处理的仓鼠体重出现预期的季节性下降，但损伤组的体重保持不变，与长日照研究相同。由于暗期进食次数增加和亮期进食量减少，损伤组仓鼠在暗期早期进食较多，在亮期进食较少，因此它们在其巢箱中的累积食物摄入量大于对照组仓鼠。总之，在后下丘脑的食欲素反应性细胞消融通过防止季节性摄食量减少来阻止短日照引起的体重下降，这一证据与中枢组胺能机制有助于体重的长期调节的假说一致。
