Louisiana State University Health Sciences Center, New Orleans, La 70112-1393, USA.
Neuroendocrinology. 2010;91(1):48-55. doi: 10.1159/000262446. Epub 2009 Nov 26.
The cachexia-anorexia syndrome, in which patients suffering from chronic illness lack the desire to eat and experience weight loss, creates a serious clinical problem when patients are attempting to overcome the disease process. Endotoxin (ET) has many actions in the brain and peripheral injections can affect regulation of monoamines in brain areas as diverse as the olfactory lobes and the locus coeruleus. Certainly, ET is involved in the febrile process and it plays a prominent role in the regulation of food intake and maintenance of body weight during chronic illnesses. Monoamine neurotransmitters in specific regions of the hypothalamus also participate in the regulation of food intake and body weight and have been well characterized. In this regard, the hypothalamic perifornical nucleus (PFN) is of interest to our lab due to its role in drug-induced anorexia caused by amphetamines. It is also the most sensitive site in the hypothalamic monoaminergic system that involves dopamine (DA) and epinephrine (EPI). DA antagonist, stereotaxically placed in this site, can stimulate feeding, and specific injections of DA or EPI can result in a 70-90% decrease in food intake, even in food-deprived animals. We have shown in our studies that ET in a dose (0.2 mg/kg of lipopolysaccharide) that does not induce noticeable ambulatory (lack of movement) effects (related to malaise) can cause a significant decrease in food intake in lean Zucker rats. We hypothesize that exogenous ET causes an increase in the extracellular concentrations of monoamines in the perifornical hypothalamus, which in turn can mediate the decrease in food intake. Microdialysis was utilized to measure extracellular concentrations of EPI, norepinephrine, 5-hydroxyindoleacetic acid, DA, and serotonin or 5-hydroxytryptamine. These measurements were taken at a post-ET time period that coincides with an ET-induced decrease (4x) in food intake. Extracellular DA and EPI both significantly increased in the PFN in response to injection of ET. Increases in extracellular DA were dose related and were significant (p < 0.05) compared to zero baseline and saline at both doses of ET. No statistically significant differences were found in 5-hydroxyindoleacetic acid, norepinephrine, and serotonin in microdialysates of this part of the hypothalamus. The present data suggest that catecholamines, namely DA and EPI which are known to decrease food intake, in the PFN may be involved in the regulation of decreases in food intake caused by peripherally administered ET. This does not rule out a role for locally produced inflammatory molecules in the brain in this process.
恶病质-厌食症综合征，即患有慢性疾病的患者缺乏食欲并导致体重减轻，当患者试图克服疾病过程时，会造成严重的临床问题。内毒素 (ET) 在大脑中有多种作用，外周注射会影响嗅觉叶和蓝斑等不同脑区中单胺的调节。当然，ET 参与发热过程，在慢性疾病期间，它在调节食物摄入和维持体重方面起着突出作用。下丘脑特定区域的单胺能神经递质也参与食物摄入和体重的调节，并已得到很好的描述。在这方面，由于其在安非他命引起的药物诱导性厌食症中的作用，下丘脑外侧核（PFN）引起了我们实验室的兴趣。它也是涉及多巴胺 (DA) 和去甲肾上腺素 (EPI) 的下丘脑单胺能系统中最敏感的部位。立体定向放置在此部位的 DA 拮抗剂可刺激进食，而特定的 DA 或 EPI 注射可导致食物摄入量减少 70-90%，即使在饥饿的动物中也是如此。我们在研究中表明，在不会引起明显运动（与不适相关）效果的剂量（0.2 毫克/千克脂多糖）下，ET 可以导致瘦 Zucker 大鼠的食物摄入量显著减少。我们假设外源性 ET 导致外侧下丘脑中单胺类物质的细胞外浓度增加，这反过来又可以介导食物摄入量的减少。微透析用于测量 EPI、去甲肾上腺素、5-羟吲哚乙酸、DA 和血清素或 5-羟色胺的细胞外浓度。这些测量是在 ET 诱导的食物摄入量减少（4 倍）后的时间点进行的。ET 注射后，PFN 中的细胞外 DA 和 EPI 均显着增加。细胞外 DA 的增加与剂量有关，与零基线和 ET 两种剂量的生理盐水相比均有统计学意义（p < 0.05）。在该下丘脑部位的微透析物中，未发现 5-羟吲哚乙酸、去甲肾上腺素和血清素有统计学意义的差异。目前的数据表明，PFN 中的儿茶酚胺，即众所周知的降低食物摄入的 DA 和 EPI，可能参与了外周给予 ET 引起的食物摄入减少的调节。这并不排除脑内局部产生的炎症分子在这一过程中的作用。
