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Overall ultrastructure of human myenteric ganglia. a Overall TEM view of a myenteric ganglion. Myenteric ganglia are located between the longitudinal and circular muscular layers (m). Neurons (n) are characterized by a voluminous nucleus with prominent nucleoli. They are less numerous than glial cells (g). Interstitial Cells of Cajal (ICCs) are surrounding enteric ganglia and nervous tracts. b An enteric neuron in straight relation with two glial cells (g). c ICCs between two nervous tracts. Glial cells are enveloping axons (ax) forming unmyelinated nerves
Source publication
Adult neurogenesis has been profusely studied in central nervous system. However, its presence in enteric nervous system remains elusive although it has been recently demonstrated in mice and intimately linked to glial cells. Moreover, primary cilium is an important organelle in central adult neurogenesis. In the present study, we analysed some par...
Citations
... Neurons crosstalk with non-neuronal cells such as glia (Alvarez-Maubecin et al., 2000;Iruzubieta et al., 2020), ICCs (Vannucchi, 1999;Iruzubieta et al., 2020), and immune cells (Muller et al., 2020;Jacobson et al., 2021). The AAV-labeling has advantage to elucidate innervation to non-neuronal cells. ...
... Neurons crosstalk with non-neuronal cells such as glia (Alvarez-Maubecin et al., 2000;Iruzubieta et al., 2020), ICCs (Vannucchi, 1999;Iruzubieta et al., 2020), and immune cells (Muller et al., 2020;Jacobson et al., 2021). The AAV-labeling has advantage to elucidate innervation to non-neuronal cells. ...
... It is documented that ICC in different intestinal layers have distinct morphologies and functions (Vannucchi, 1999;Al-Shboul, 2013;Pasternak et al., 2016), and their levels decreased with aging, inflammatory diseases, and constipation (Huizinga and Chen, 2014). Some ICC are located between autonomic nerve endings and smooth muscular cells to form connections with extrinsic neurons (Vannucchi, 1999;Blair et al., 2012;Al-Shboul, 2013;Huizinga and Chen, 2014) and surround enteric ganglia and nerve tracts in human myenteric plexus as visualized by electromicroscopy and 3D reconstruction (Iruzubieta et al., 2020). The evidence of some ICC contact nerves, macrophages and smooth muscle cells (Schneider et al., 2019;Iruzubieta et al., 2020) supports that there is a subclass of ICC playing a role in communication among different types of cells. ...
Systemic delivery of adeno-associated virus (AAV) vectors transduces the enteric nervous system. However, less is known on the mapping and morphological and neurochemical characterization in the adult mouse colon. We used AAV9-CAG-GFP (AAV9) and AAV-PHP.S-hSyn1-tdTomato farnesylated (PHP.S-tdTf) to investigate the segmental distribution, morphologies and neurochemical coding of the transduction. The vectors were retro-orbitally injected in male and female adult mice, and 3 weeks later, the colon was prepared for microcopy with or without immunohistochemistry for neuronal and non-neuronal markers. In contrast to the distributions in neonatal and juvenile rodents, the AAV transduction in neurons and/or nerve fibers was the highest in the proximal colon, decreased gradually in the transverse, and was sparse in the distal colon without difference between sexes. In the proximal colon, the AAV9-transduced myenteric neurons were unevenly distributed. The majority of enteric neurons did not have AAV9 expression in their processes, except those with big soma with or without variously shaped dendrites, and a long axon. Immunolabeling demonstrated that about 31% neurons were transduced by AAV9, and the transduction was in 50, 28, and 31% of cholinergic, nitrergic, and calbindin-positive myenteric neurons, respectively. The nerve fiber markers, calcitonin gene-related peptide alpha, tyrosine hydroxylase or vasoactive intestinal polypeptide co-localized with AAV9 or PHP.S-tdTf in the mucosa, and rarely in the myenteric plexus. Unexpectedly, AAV9 expression appeared also in a few c-Kit immunoreactive cells among the heavily populated interstitial cells of Cajal (ICC). In the distal colon, the AAV transduction appeared in a few nerve fibers mostly the interganglionic strands. Other types of AAV9 and AAV-PHP vectors induced a similar colonic segmental difference which is not colon specific since neurons were transduced in the small intestine and gastric antrum, while little in the gastric corpus and none in the lower esophagus.
Conclusion
These findings demonstrate that in adult mice colon that there is a rostro-caudal decrease in the transduction of systemic delivery of AAV9 and its variants independent of sex. The characterization of AAV transduction in the proximal colon in cholinergic and nitrergic myenteric neurons along with a few ICC suggests implications in circuitries regulating motility.
Of all the organ systems in the body, the gastrointestinal tract is the most complicated in terms of numbers of the structures involved, each with different functions, and the numbers and types of signaling molecules utilized. The digestion of food and absorption of nutrients, electrolytes and waters occurs in a hostile luminal environment that contains a large and diverse microbiota. At the core of regulatory control of the digestive and defensive functions of the gastrointestinal tract is the enteric nervous system (ENS), a complex system of neurons and glia in the gut wall. In this review, we discuss (i) the intrinsic neural control of gut functions involved in digestion, and (ii) how the ENS interacts with the immune system, gut microbiota and epithelium to maintain mucosal defense and barrier function. We highlight developments that have revolutionized our understanding of the physiology and pathophysiology of enteric neural control. These include the molecular architecture of the ENS, the organization and function of enteric motor circuits, and the roles of enteric glia. We explore the transduction of luminal stimuli by enteroendocrine cells, the regulation of intestinal barrier function by enteric neurons and glia, local immune control by the ENS and the role of the gut microbiota in regulating the structure and function of the ENS. Multifunctional enteric neurons work together with enteric glial cells, macrophages, interstitial cells and enteroendocrine cells integrating an array of signals to initiate outputs that are precisely regulated in space and time to control digestion and intestinal homeostasis.
This special Issue presents comprehensive and state-of-the-art advances in supporting the crucial role of the bidirectional interactions between the Brain-Gut Axis in health and diseases with an emphasis on the microbiome-gut-brain axis and its implications in variety of neurological disorders. Graphic Abstract: There are intimate connections between the brain and the digestive system. Gut microbiota dysbiosis activates the intestinal immune system, enhances intestinal permeability and bacterial translocation, leading to neuroinflammation, epigenetic changes, cerebrovascular alterations, amyloid β formation and α-synuclein protein aggregates. These alterations may participate in the development of hypertension, Alzheimer, Parkinson, stroke, epilepsy and autism. Brainstem nuclei such as the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) regulate gastric motor function by way of bidirectional inputs through the vagus nerve.[Figure not available: see fulltext.] © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
