• Conference poster

Age-related loss of GPR68 and calretinin immunoreactive neurons within the mucosa, not the myenteric plexus of human colon

Baidoo, N. 2025. Age-related loss of GPR68 and calretinin immunoreactive neurons within the mucosa, not the myenteric plexus of human colon. Neurogastroenterology Meeting 2025. London 04 - 06 Sep 2025 Wiley.

TitleAge-related loss of GPR68 and calretinin immunoreactive neurons within the mucosa, not the myenteric plexus of human colon
AuthorsBaidoo, N.
TypeConference poster
Abstract

Background: The G protein-coupled receptor 68 (GPR68) detects variations in extracellular pH, and has potential roles in homeostasis and responses to ischemia and inflammation within different organs, including the gastrointestinal tract. However, in the human colon the distribution of GPR68 remains unclear. We examined the localization and density of GPR68 within the enteric nervous system of ascending (AC) and descending (DC) human colon from younger and older adults.
Methods: Macroscopically normal AC and DC were obtained from patients undergoing lower bowel cancer resection (aged 22–91 years; grouped into younger (≤ 60 years) and older (≥ 67 years) populations). Immunolabelling was performed using formalin-fixed, paraffin-embedded sections and antibodies against GPR68, protein gene product 9.5 (PGP9.5) and calretinin to identify the presence and density of GPR68-immunoreactive (IR) expressing cells. Images were analysed using ImageJ.
Results: Ageing did not change the density of total PGP9.5-IR enteric neuronal fibres in the AC or DC. For the myenteric plexus (MP) of both age groups, the densities of calretinin-IR neurons were similar in both the AC (younger adult: 1.2 ± 0.3 x 10-3; older: 0.9 ± 0.2 x 10-3 per mm² plexus) and DC (1.4 ± 0.2 x 10-3; 1.3 ± 0.3 x 10-3 per mm² plexus), but reduced in the mucosa of older adults for both AC (respectively, 9.8 ± 0.5 vs. 3.2 ± 0.1/pixel) and DC (11.5 ± 0.9 vs. 7.4 ± 0.3/pixel). Similar reduction of calretinin-IR enteric neurons was found in the SMP of AC but not clearly in the DC in the older adults.
GPR68 was widely expressed in the mucosa, circular muscle and myenteric plexus of both the AC and DC. The density of GPR68-IR in the muscle and myenteric plexus was similar in both age groups, but smaller in the mucosa of older adults for both AC and DC.
Conclusion: GPR68 is widely distributed within the enteric nervous system of the human colon, with potential roles for GPR68 suggested in the muscle and MP, and in the functions of calretinin-IR neurons within the mucosa. Further, the concomitant loss of GPR68 and calretinin-IR neurons in the mucosa of older adults suggests selective vulnerability of mucosal sensory and homeostatic mechanisms of the ageing colon.

KeywordsAgeing, calretinin, enteric neurons, human colon, G protein-coupled receptor 68, PGP9.5
Year2025
ConferenceNeurogastroenterology Meeting 2025
PublisherWiley
Publisher's version
File Access Level
Open (open metadata and files)
Publication dates
Published04 Sep 2025
JournalNeurogastroenterology & Motility
File
File Access Level
Open (open metadata and files)

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