Enteric Glia: S100, GFAP, and Beyond

Abstract

Since several years, the enteric nervous system (ENS) is getting more and more in the focus of gastrointestinal research. While the main interest was credited for years to the enteric neurons and their functional properties, less attention has been paid on the enteric glial cells (EGCs). Although the similarity of EGCs to central nervous system (CNS) astrocytes has been demonstrated a long time ago, EGCs were investigated in more detail only recently. Similar to the CNS, there is not "the" EGC, but also a broad range of diversity. Based on morphology and protein expression, such as glial fibrillary acidic protein (GFAP), S100, or Proteolipid-protein-1 (PLP1), several distinct glial types can be differentiated. Their heterogeneity in morphology, localization, and transcription as well as interaction with surrounding cells indicate versatile functional properties of these cells for gut function in health and disease. Although NG2 is found in a subset of CNS glial cells, it did not colocalize with the glial marker S100 or GFAP in the ENS. Instead, it in part colocalize with PDGFRα, as it does in the CNS, which do stain fibroblast-like cells in the gastrointestinal tract. Moreover, there seem to be species dependent differences. While GFAP is always found in the rodent ENS, this is completely different for the human gut.Only the compromised human ENS shows a significant amount of GFAPpositive glial cells. So, in general we can conclude that the EGC population is species specific and as complex as CNS glia. Anat Rec, 302:1333Rec, 302: -1344Rec, 302: , 2019.

Neural crest derivatives and neuroendocrine cells in the gut of anencephalic and fetuses without congenital defects

“…EGC in humans express S100a and S100b (Fu et al, 2004). EGC, analogous to the glia of the central nervous system, maintain a close relation with ENS neurons, supporting them with nutrients and neurotransmitter precursors; EGC also regulate epithelial permeability and modulate immune response (Grundmann et al, 2019). S‐100 a/b expression on the gut wall is observed toward the 12th DW and gradually intensifies, reaching its peak toward the middle of the second trimester (15th–22nd DW) (Grundmann et al, 2019).…”

“…EGC, analogous to the glia of the central nervous system, maintain a close relation with ENS neurons, supporting them with nutrients and neurotransmitter precursors; EGC also regulate epithelial permeability and modulate immune response (Grundmann et al, 2019). S‐100 a/b expression on the gut wall is observed toward the 12th DW and gradually intensifies, reaching its peak toward the middle of the second trimester (15th–22nd DW) (Grundmann et al, 2019). S‐100 expression has been observed to be mostly limited to the myenteric plexus at the 15th DW while being highly positive on the submucous and myenteric plexuses toward the 22nd DW (Grundmann et al, 2019).…”

“…S‐100 a/b expression on the gut wall is observed toward the 12th DW and gradually intensifies, reaching its peak toward the middle of the second trimester (15th–22nd DW) (Grundmann et al, 2019). S‐100 expression has been observed to be mostly limited to the myenteric plexus at the 15th DW while being highly positive on the submucous and myenteric plexuses toward the 22nd DW (Grundmann et al, 2019). Findings on our FWCD samples were similar, with the youngest samples (16 WG) showing only myenteric S‐100 reactivity and the eldest showing reactivity on both plexuses (Tables 2 and 3).…”

Enteric glial cells respond to a dietary change in the lamina propria in a MyD88-dependent manner

“…However, our current understanding of the physiological significance of EGC diversification remains unclear. EGCs play important roles in regulating intestinal motility and are even thought to be important in regulating epithelial barrier function, although the latter is still controversial (9, 19, 22). EGCs can engage functional crosstalk with all the different cell types present in the gut wall, including intestinal neurons, gut epithelium, enteroendocrine cells and immune cells, via direct physical contact or indirect paracrine secretions (28).…”

Introduction: Thematic Papers Issue on “Advances in Our Understanding of the Morphological Response to Injury in the Peripheral Nervous System”

“…Finally, David Grundmann and colleagues (Grundmann et al, , this issue) present novel aspects of ENS plasticity, with particular reference to enteric glia. For years, these cells have played a “wallflower”‐like role, although their importance was already recognized by several authors who demonstrated that enteric glia, just like reactive astrocytes in the central nervous system, contain glial fibrillary acidic protein.…”