Enhanced pelvic responses to stressors in female CRF-overexpressing mice

Abstract

Acute stress affects gut functions through the activation of corticotropin-releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in the context of chronic stress is not well characterized. We investigated the colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO), urine voiding, and ambulatory activity, respectively, in female and male CRF-overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2-min handling (150%) and 60-min novel environment (155%) but displayed a similar response to a 60-min partial restraint stress. Female CRF-OE mice, compared with WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs. 1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/- 31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded to a novel environment but failed to show differences between them in colonic and locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%). In female CRF-OE mice, the CRF(1)/CRF(2) receptor antagonist astressin B and the selective CRF(2) receptor agonist mouse urocortin 2 (injected peripherally) prevented the enhanced defecation without affecting urine or locomotor responses to novel environment. RT-PCR showed that CRF(1) and CRF(2) receptors are expressed in the mouse colonic tissues. The data show that chronic stress, due to continuous central CRF overdrive, renders female CRF-OE mice to have enhanced pelvic and altered behavioral responses to superimposed mild stressors and that CRF(1)-initiated colonic response is counteracted by selective activation of CRF(2) receptor.

Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors

“…Astressin B selectively blocked the initial robust stress-induced response without affecting the later lower response. Similar blockade by astressin B of the initial high colonic motor response to stress, without affecting the subsequent basal like response, are well documented (28,35). The evidence that astressin does not have effect on basal colonic motor activity (28, 34 -36), coupled with the present data in which astressin B blocked the initial robust response without affecting the subsequent 20-to 60-min period response, suggests that the later non-astressin B-sensitive low and stable contractile pattern may represent a basal type of activity.…”

“…Previous studies have shown that over 80% of the fecal pellet output response to acute stress occurs in the first 30 min of the stress sessions (28,34,35). In the present study setting, colonic contractile response was continuously recorded for 60 min.…”

“…Restraint consisted of placing each mouse, for a 60-min period, in a Falcon plastic tube (2.7 cm diameter, 7-10 cm long, BD, Franklin Lakes, NJ) with several holes on the side and front for adequate ventilation (partial restraint tube device) as previously described (28,35). The dimensions of the tube prevented the mice from turning around and limited their ability to move forward or backward.…”

“…This provided a representative value of the initial activation of colonic motility in response to acute stress and thus allows intraindividual comparison among mice. The reasons for making a correlation study between the 60-min fecal pellet output and the first 20 min of normalized colonic contractions are that 1) because the presence of catheters in the colon in the RS conscious mice, fecal pellet output can only be measured at the end of the stress session (60 min); 2) several studies have shown that more than 80% of fecal pellet output induced by RS in rats and mice occurred in the first 30 min of the stress session (28,34,35); and 3) the present data show that the robust colonic contractile response to RS occurs in the first 20-min period, in agreement with the second point above. Thus to validate the use of miniature pressure transducer solid-state manometry to monitor propulsive colonic motility, we assessed whether there was a correlation between the first 20 min of colonic contractions with the classic colonic propulsive assay, the 60-min fecal pellet output.…”

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…Genetic model of depression or anxiety, such as the high-anxiety Wistar-Kyoto (WKY) rats or Flinders Sensitive Line rats have shown increased sensitivity to colorectal distension (Overstreet and Djuric 2001). In the same way genetic models deleting CRF1 exhibit a decrease in colonic sensitivity to colonic distension (Trimble, et al 2007) while models overexpressing CRF1 exhibit enhanced response to colonic distension (Million, et al 2007). These data argue for the filiation stress-anxietyinflammation and visceral hypersensitivity.…”