Long-term effect of parasympathetic or sympathetic denervation on intestinal epithelial cell proliferation and apoptosis

Abstract

This study investigates the long-term effect of autonomic denervation on intestinal epithelial cell turnover, as measured by proliferation, apoptosis, and total cell number. Although previous research has established that autonomic denervation can alter intestinal epithelial turnover under short-term conditions, here we establish for the first time that these changes do not persist long-term when you control for surgical-induced changes in food intake and use targeted denervation procedures. These findings add to the base of knowledge on autonomic control of tissue turnover, highlight the ability of the intestinal epithelium to recover after autonomic injury and reveal possible implications of the use of ANS denervation for disease treatment in humans. AbstractIntestinal epithelial tissue is constantly regenerated as a means to maintain proper tissue function. Previous studies have demonstrated that denervation of the parasympathetic or sympathetic nervous system to the intestine alters this process. However, results are inconsistent between studies, showing both increases and decreases in proliferation after denervation of the parasympathetic or sympathetic. The effect appears to correlate with (1) the timing post-denervation, (2) denervation-induced changes in food intake, (3) the denervation technique used, and (4) which intestinal segment is investigated. Thus, we proposed that parasympathetic or sympathetic denervation does not have an effect on intestinal epithelial regeneration when you (1) evaluate denervation after long-term denervation, (2) control for post-surgical changes in food intake, (3) use minimally invasive surgical techniques and (4) include a segmental analysis. To test this, adult male Sprague Dawley rats underwent parasympathetic denervation via subdiaphragmatic vagotomy, sympathetic denervation via celiacomesenteric ganglionectomy, a parasympathetic denervation sham surgery, or a sympathetic denervation sham surgery. Sham surgery ad libitum-fed groups and sham surgery pair-fed groups were used to control for surgically induced changes in food intake. Three weeks post-surgery, animals were sacrificed and tissue from the duodenum, jejunum, and ileum was excised and immunohistochemically processed to visualize indicators of proliferation (bromodeoxyuridine-positive cells) and apoptosis (caspase-3-positive cells). Results showed no differences between groups in proliferation, apoptosis, or total cell number in any intestinal segment. These results suggest that parasympathetic or sympathetic denervation does not have a significant long-term effect on intestinal epithelial turnover. Thus, intestinal epithelial regeneration is able to recover after autonomic nervous system injury.

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

“…These results indicate that the vagus nerve is required for the orexigenic effects of ghrelin when tested during the natural rodent feeding cycle (onset of dark cycle). SDV animals weighed significantly less than sham animals at the start of the IP ghrelin experiment (Sham: 409.8g +/-8.5; SDV: 362.6g +/-9.5; p<0.05) even after an extended post-surgical recovery period, as we have previously shown [25]. However, while SDV animals ate significantly less overall compared with the sham animals ( Fig.…”

“…These findings are consistent with a previous report by Date et al [7], which found that both SDV and chemical vagal deafferentation attenuate the hyperphagic effect of ghrelin. However, in the study by Date and colleagues the evaluation of ghrelin-stimulated hyperphagia occurred before the complete recovery from SDV surgery, which is critical for the return to feeding behavior and other physiological functions after vagotomy [25,[49][50][51]. In contrast, Arnold et al, reported that SDV has no effect on ghrelin-mediated hyperphagia in rats [52].…”

Neuroimmune Interactions in the Gut and Their Significance for Intestinal Immunity

“…After SNS or PNS denervation, epithelial cell proliferation has either decreased [130,133,134,135] or increased [136]. Results are time dependent and effects seem to recover due to compensatory mechanisms, such as upregulation of adrenergic or cholinergic receptor expression, compensation by non-denervated branch, and modulation of the ENS [137]. No data exist on a change in epithelial cell proliferation after sympathetic or parasympathetic stimulation, rather than denervation.…”

Isoprenaline protects intestinal stem cells from chemotherapy‐induced damage

“…These data indicated that blocking the SNS decreased proliferation and differentiation of intestinal stem cells. Experiments using pharmacological and surgical approaches to disrupting the SNS, showed that disruption of the SNS or the PNS, either decreased or increased mitotic rates, depending on the time frame of drug action (Davis et al, 2017). These results indicate that the autonomic nervous system can affect the mitotic kinetics of intestinal epithelial cells under physiological and pathological conditions.…”