Prenatal alcohol exposure reduces 5-HT concentration in mouse intestinal muscle and mucosa

Abstract

The influence of prenatal alcohol exposure on the serotoninergic system in the brain has been well studied, however its influence on the serotoninergic system in the gastrointestinal system remains unknown. The objective of the study was to use a mouse model of prenatal alcohol exposure to investigate the effects on serotonin and its metabolites and precursors in colonic tissue. This study used treatment of mouse breeding harems with 5% ethanol with saccharin via drinking water throughout pregnancy and compared the results with a saccharin control group. Tryptophan, serotonin (5-HT) and 5- hydroxyindoleacetic acid (5-HIAA) concentrations were measured in the longitudinal muscle myenteric plexus (LMMP) and mucosa of intestinal tissue by high-performance liquid chromatography (HPLC). Decreased 5-HT concentrations in mucosa and LMMP (females only) were observed in prenatally exposed mice compared to controls. Increases in mucosal and LMMP tryptophan concentration were only observed in prenatally exposed female mice. In conclusion, prenatal alcohol exposure causes a decrease in conversion of tryptophan to 5-HT in both muscle and mucosa although the effect is more pronounced in females. The observed sex difference may be related to changes associated with the estrous cycle.

Prenatal ethanol exposure causes anxiety-like phenotype and alters synaptic nitric oxide and endocannabinoid signaling in dorsal raphe nucleus of adult male rats

“…Serotonin neurons of the dorsal raphe nucleus (DRn), which provide the bulk of 5-HT in the brain [ 15 ] develop early during embryogenesis (E11-E15) [ 16 ] and are vulnerable to the teratogenic effects of ethanol. Indeed, animal studies have reported that PE reduces the development of 5-HT neurons [ 17 , 18 ], decreases 5-HT projections [ 19 , 20 ], reduces tryptophan hydroxylase type 2 (Trph2) [ 21 ] and 5-HT levels in the brain [ 17 , 22 ]. These developmental alterations contribute, at least in part, to anxiety-like behaviors in PE rats [ 23 ].…”

A Healthy Gut for a Healthy Brain: Preclinical, Clinical and Regulatory Aspects

“…Indeed, the global prevalence of FASD is about 2-4% in the newborns [ 199 ]. A study in the mouse [ 200 ] on the influence of prenatal alcohol exposure on the serotoninergic system in the gastrointestinal system disclosed decreased serotonin concentrations in the gut mucosa and longitudinal muscle myenteric plexus (females only). Furthermore, an elevation in mucosal and longitudinal muscle myenteric plexus tryptophan concentration was only observed in prenatally exposed female mice.…”

“…Furthermore, an elevation in mucosal and longitudinal muscle myenteric plexus tryptophan concentration was only observed in prenatally exposed female mice. These findings show that prenatal alcohol exposure may elicit a decrease in the conversion of tryptophan to serotonin in both muscle and mucosa, effect more pronounced in females, changes probably associated with the estrous cycle [ 200 ]. Other earlier human and animal model studies clearly demonstrated that prenatal alcohol exposure affects intestine formation/functioning development and nutrients absorption [ 190 , 201 - 203 ].…”

A microfluidic chip for sustained oxygen gradient formation in the intestine ex vivo

“…To recapitulate the intestine ex vivo, biological models such as 2D or 3D cell culture, 21,22 tissue sections, 15,17,23,24 and tissue slices 25,26 enables specific subsets of cells to be probed without interference from unwanted cells; 27 however, the importance of the cellular distribution, morphology, and environmental conditions has become apparent in the intestine leading to the adaptation of 3D cell culture. 28,29 Prior work has demonstrated a device designed to incorporate a curved scaffolding for the cells of interest to be seeded onto: this recreates the general intestinal structure for in vitro analysis.…”

“…To recapitulate the intestine ex vivo , biological models such as 2D or 3D cell culture, 21,22 tissue sections, 15,17,23,24 and tissue slices 25,26 have been explored. 2D cell culture enables specific subsets of cells to be probed without interference from unwanted cells; 27 however, the importance of the cellular distribution, morphology, and environmental conditions has become apparent in the intestine leading to the adaptation of 3D cell culture.…”