Is Neuronal Histamine Signaling Involved in Cancer Cachexia? Implications and Perspectives

In this paper, we present evidence in support of our hypothesis that the neuronal histaminergic system might be involved in cancer cachexia1. To build our premise, we present the research and the reasonable inferences that can be drawn from it in a section by section approach starting from one of the key issues related to cachexia, increased resting energy expenditure (REE), and progressing to the other, anorexia. Based on an extensive survey of the literature and our own deliberations on the abovementioned topics, we investigate whether histamine signaling might be the mechanism used by a tumor to hijack the body's thermogenic machinery. Our hypothesis in short is that hypothalamic histaminergic neurons are stimulated by inputs from the parasympathetic nervous system (PSNS), which senses tumor traits early in cancer development. Histamine release in the preoptic area of the hypothalamus primarily activates brown adipose tissue (BAT), triggering a highly energy demanding mechanism. Chronic activation of BAT, which, in this context, refers to intermittent and/or low grade activation by the sympathetic nervous system, leads to browning of white adipose tissue and further enhances thermogenic potential. Aberrant histamine signaling not only triggers energy-consuming processes, but also anorexia. Moreover, since functions such as taste, smell, and sleep are governed by discrete structures of the brain, which are targeted by distinct histaminergic neuron populations even relativel...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research