Neurons populating the rectal extrinsic nerves in humans express neuronal and Schwann cell markers

• Published in: Neurogastroenterology and motility 2021-07, Vol.33 (7), p.e14074-n/a
• Main Authors: Woods, Crystal, Kapur, Raj P., Bischoff, Andrea, Lovell, Mark, Arnold, Michael, Peña, Alberto, Flockton, Amanda, Sharkey, Keith A., Belkind‐Gerson, Jaime
• Format: Article
• Language: English
• Subjects: Adolescent; Anorectal; anorectal malformation; Anorectal Malformations; Antigens; Autonomic nervous system; Autopsy; Cadavers; Cell migration; Child; Child, Preschool; Children; Digestive system; enteric glia; Enteric nervous system; Female; Ganglion cells; Gastrointestinal tract; Hirschsprung disease; Humans; Immunohistochemistry; Infant; Infant, Newborn; Innervation; Male; Myelin proteolipid protein; Neural stem cells; Neural Stem Cells - physiology; Neurogenesis; Neurogenesis - physiology; Neuronal-glial interactions; neurons; Progenitor cells; Rectum; Rectum - innervation; Schwann cells; Schwann Cells - cytology; Sox10 protein
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.14074

Background In mice, Schwann cell (SC) progenitors give rise to autonomic ganglion cells and migrate into the gut to become enteric neurons. It is unknown whether SC progenitors have a similar fate in humans. In search of evidence for human SC‐derived neurogenesis in the gastrointestinal (GI) tract, we studied the rectums from cadaveric controls and children with anorectal malformations (ARM). Methods We analyzed distal rectal tissue taken at autopsy from 10 children with normal GI tracts and resected rectal specimens in 48 cases of ARM. Of these specimens, 6 had neurons within the extrinsic rectal innervation. These were further investigated with immunohistochemistry for neuronal and SC/glial markers. Key Results Perirectal tissue from control and ARM contained GLUT1‐positive extrinsic nerves, many containing neurons. SC/glial markers (SOX10, CDH19, and PLP1) were expressed by glia in the enteric nervous system and perirectal nerves, while MPZ predominated only in glia of perirectal nerves, in both control and ARM. Neurons in perirectal nerves were 61% larger in ARM samples and co‐expressed SOX10 (81%), PLP1 (73%), and CDH19 (56%). In ARM, cytoplasmic SOX10 was co‐expressed with neuronal antigens in ~57% of submucosal and myenteric neurons, vs. ~3% in control. Furthermore, intrinsic gut neurons in ARM specimens co‐expressed PLP1 (18%) and CDH19 (18%); however, neuronal co‐expression of PLP1 and CDH19 was rarely (