Laboratory of Neuroimmunology and Behavior, Center for the Study of Complementary and Alternative Therapies, University of Virginia School of Nursing, P.O. Box 800782 Charlottesville, VA 22908-0782, USA.
Brain Res. 2009 Oct 19;1294:61-79. doi: 10.1016/j.brainres.2009.07.076. Epub 2009 Jul 30.
Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge engages multiple ascending neural pathways including both a distinct catecholaminergic "danger" pathway, and a possibly multimodal pathway derived from the NTS.
尾侧脑干内脏感觉核将有关身体内部状态的信息传递到涉及进食行为和对免疫挑战反应的前脑区域，并可能在免疫激活后调节摄食行为。疾病引起的食欲减退可能归因于增强的“饱腹感”途径，与饱腹感途径分开的独特“危险通道”的激活，或两者兼有。为了评估可能介导疾病对摄食行为影响的神经基质，我们分析了对消耗喜爱食物（加糖牛奶）以及对腹膜内脂多糖挑战（降低加糖牛奶摄入量）有反应的髓质神经元的模式和表型。脑桥切片用 c-Fos、多巴胺β-羟化酶、苯乙醇胺-N-甲基转移酶和胰高血糖素样肽-1 (GLP-1) 免疫反应性染色。加糖牛奶的摄入激活了孤束核 (NTS) 中的许多神经元，包括 NTS 尾部的 A2 去甲肾上腺素能神经元。LPS 挑战除了在 NTS 中激活了类似的神经元群外，还激活了 NTS 中的 C2 肾上腺素能神经元和中间的 A2 去甲肾上腺素能神经元、腹外侧髓质中的许多 C1 和 A1 神经元，以及背侧髓质网状核中的 GLP-1 神经元。NTS 中激活的 GLP-1 神经元数量的增加仅与加糖牛奶的摄入有关。平行处理的证据反映在臂旁核中，其中加糖牛奶的摄入导致内外部外侧、腹外侧和中央内侧部分的激活，而 LPS 挑战则在外部外侧部分诱导 c-Fos 表达。因此，对潜在危险生理状况的反应生成的信号似乎通过 NTS 和 VLM 中的特定儿茶酚胺能神经元传播，并可能包括通过外部外侧 PBN 的途径。数据表明，免疫挑战涉及多个上行神经通路，包括独特的儿茶酚胺“危险”通路，以及可能源自 NTS 的多模态通路。
