The Gut-Brain Axis
Elizabeth is a fourth year PhD candidate in Megan Dailey's lab. Elizabeth's dissertation focuses on the autonomic influence on intestinal epithelial stem cell proliferation. Her favorite brain region is the nucleus of the solitary tract.
More than “fight or flight” and “rest and digest”: the sympathetic (SNS) and parasympathetic (PNS) nervous system control of stem cell proliferation and tissue regeneration
The central nervous system is connected to the gastrointestinal tract through its autonomic connections. These efferent projections of the sympathetic and parasympathetic nerves have been identified to play a role in a number of gastrointestinal functions, including epithelial proliferation and growth. It had been thought that this control was mediated indirectly through the enteric neural connections with the epithelial tissue. We found, though, that isolated IESCs and other crypt cells express receptors for SNS and PNS neurotransmitters. Furthermore, intestinal epithelial organoid proliferation in vitro was decreased in response to norepinephrine, the main postganglionic neurotransmitter of the SNS (Feldner, Davis & Dailey, 2017; Davis, Zhou & Dailey, Experimental Physiology, under review). More recent data published by other labs have also found SNS and PNS fibers in close proximity to the intestinal crypts. This suggests that SNS and PNS may directly alter intestinal epithelial proliferation, independent of its connections with the enteric nervous system (reviewed in, Davis & Dailey, American Journal of Physiology, in revision). Whether these connections or direct or indirect, manipulation of the SNS or PNS using already FDA approved devices (e.g. VBLOC) may be a way to control tissue development, regeneration and function.
The impact of autonomic nervous system denervation on tissue regeneration
Because of the importance of the renewal process in maintaining proper tissue function, we tested the effect of a loss of SNS or PNS innervation to the intestinal tract on epithelial proliferation and apoptosis. Although there are changes in the rate of tissue renewal in the first two weeks after SNS or PNS denervation surgeries, we established for the first time that these alterations do not persist long-term when you control for surgical-induced changes in food intake and use targeted denervation procedures (Davis, Washington, Yaniz, Phillips, Sayegh & Dailey, 2017). Our data support the narrative that compensatory mechanisms recover a variety of physiological functions to homeostatic levels after autonomic injury. This finding is important because autonomic denervation is currently used in human patients to treat a variety of diseases.
Evidence for a direct effect of the autonomic nervous system on intestinal epithelial stem cell proliferation. Davis EA, Zhou W, & Dailey MJ. Physiological Reports, 2018 Jun; 6(12), e13745.
Obesity, independent of diet, drives lasting effects on intestinal epithelial stem cell proliferation in mice. Zhou W, Davis EA, & Dailey MJ. Experimental Biology and Medicine, 2018 Jun; 243(10), 826-835.
Sex differences influence intestinal epithelial stem cell proliferation independent of obesity. Zhou W, Davis EA, & Dailey MJ. Physiological Reports, in press.
Long-term effect of parasympathetic or sympathetic denervation on intestinal epithelial cell proliferation and apoptosis. Davis EA, Washington MC, Yaniz ER, Phillips H, Sayegh AI, Dailey MJ. Exp Biol Med. 2017 Sep; 242(15):1499-1507.
Alpha2A adrenoreceptor influence on intestinal epithelial stem cell proliferation. Feldner MKE, Davis EA, Dailey MJ. iACES. 2017 Apr; 3:6-11.
Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals. Kreisler AD, Davis EA, and Rinaman L. Physiol Behav. 2014 Sep; 136:47-54.