Lack of serotonin 5-HT_2Breceptor alters proliferation and network volume of interstitial cells of Cajalin vivo

Abstract

Background-Normal gastrointestinal motility requires intact networks of interstitial cells of Cajal (ICC). ICC numbers are maintained by a balance between cell loss factors and survival/ trophic/growth factors. Activation of 5-HT 2B receptors expressed on ICC increases ICC proliferation in vitro. It is not known whether 5-HT 2B receptors on ICC are activated in vivo. The aims of this study were to investigate if adult ICC proliferate, whether the proliferation of ICC in vivo is affected by knocking out the 5-HT 2B receptor, and if alterations in proliferation affect ICC networks.

Interstitial cells of Cajal — systematic review

“…We know also, playing similar role, other signal paths with neuronal originated nitric oxide [5], serotonin acting through 5-HT 2B receptor [68], interleukine-9 [70], insulin and insulin-like growth factor (IGF-1) [21], heme oxygenase (HO-1) [4]. 5-HT 2B receptor is responsible for maintenance of network of ICC [59]. Its activation begins proliferation of ICC.…”

Numerical metrics for automated quantification of interstitial cell of Cajal network structural properties

“…ICC express 5-HT 2B receptors, and stimulation with 5-HT (serotonin) increases ICC proliferation and numbers [27]. It has also been demonstrated that a lack of 5-HT 2B receptors decrease ICC proliferation, numbers and network volume [19]. These images were 512 Â 512 pixels, and represented physical dimensions ranging from 0.225 Â 0.225 mm to 0.318 Â 0.318 mm.…”

“…An ICC network image from a 5-HT 2B receptor KO jejunal ICC-MP dataset [19] was used as an example network to illustrate the developed metrics (figures 1a and 2b). See §2.2.1 for the detailed description of the example network image.…”

“…However, as ICC-MP have been identified as the primary pacemakers of slow waves in the small intestine [4], only the network structure of these cells were analysed. Two-dimensional bitmap images of the Kit-positive ICC structures were obtained as previously described [19,25]. Briefly, intestinal sections were dissected quickly, then flushed with ice-cold calciumfree Hanks balanced salt-solution (Invitrogen, Carlsbad, CA), and immediately pinned onto sylgard lined Petri dishes to mitigate against tissue deformation.…”

“…Although the complex network structures formed by ICC can be accurately imaged, current descriptors of ICC loss only involve simple cell (nuclei) counts and volume computations [17,19], and no attempts are currently made to quantify spatial changes that may be occurring in the structural properties of ICC networks. Accurately defining the structural characteristics of ICC networks would allow investigators to explicitly contrast and compare aspects of ICC organization in a consistent, unbiased manner.…”