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Two Brains Are Better Than One

Graphic source: National Cancer Institute; Public Domain, Wikipedia Commons



Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary 1) ___, which measures about nine meters end to end from the esophagus to the anus. The enteric nervous system is one of the main divisions of the nervous system and consists of a mesh-like system of neurons that governs the function of the gastrointestinal system; it has been described as a “second brain“ for several reasons. The enteric nervous system can operate autonomously. It normally communicates with the central nervous system (CNS) through the parasympathetic (e.g., via the vagus nerve) and sympathetic (e.g., via the prevertebral ganglia) nervous systems. However, vertebrate studies show that when the Vegas 2) ___ is severed, the enteric nervous system continues to function.


In vertebrates, the enteric nervous system includes efferent neurons, afferent neurons, and interneurons, all of which make the enteric nervous system capable of carrying reflexes in the absence of CNS input. The sensory neurons report on mechanical and chemical conditions. Through intestinal muscles, the 3) ___ neurons control peristalsis and churning of intestinal contents. Other neurons control the secretion of enzymes. The enteric nervous system also makes use of more than 30 neurotransmitters, most of which are identical to the ones found in CNS, such as acetylcholine, dopamine, and serotonin. More than 90% of the body’s 4) ___ lies in the gut, as well as about 50% of the body’s dopamine and the dual function of these neurotransmitters is an active part of gut-brain research. Researchers found noticeable improvements in the ability of rats to cope with stressful activity (such as swimming) when diets are supplemented by specific gut microbiota.


The gut-brain axis, a bidirectional neurohumoral communication system, is important for maintaining homeostasis and is regulated through the central and ENS 5) ___ ___ ___ and the neural, endocrine, immune, and metabolic pathways, and especially including the hypothalamic-pituitary-adrenal axis (HPA axis). That term has been expanded to include the role of the gut flora as part of the “microbiome-gut-brain axis“, a linkage of functions including the gut flora. Interest in the field was sparked by a 2004 study showing that germ-free mice (genetically homogeneous laboratory mice, birthed and raised in an antiseptic environment) showed an exaggerated HPA axis response to 6) ___ compared to non-GF laboratory mice. The gut flora can produce a range of neuroactive molecules, such as acetylcholine, catecholamines, ?-aminobutyric acid, histamine, melatonin, and serotonin, which is essential for regulating peristalsis and sensation in the gut. Changes in the composition of the gut flora due to diet, drugs, or disease correlate with changes in levels of circulating cytokines, some of which can affect brain function. The gut flora also releases molecules that can directly activate the vagus nerve which transmits information about the state of the intestines to the brain. Likewise, chronic or acutely stressful situations activate the hypothalamic-pituitary-adrenal axis, causing changes in the gut flora and intestinal epithelium, and possibly having systemic effects. Additionally, the cholinergic anti-inflammatory pathway, signaling through the vagus nerve, affects the gut epithelium and flora. Hunger and satiety are integrated in the brain, and the presence or absence of food in the gut and types of food present, also affect the composition and activity of gut 7) ___.


Scientists have made an important step in understanding the organization of nerve cells embedded within the gut that control its function — a discovery that could give insight into the origin of common gastrointestinal diseases, including irritable bowel syndrome and chronic constipation and much more. The findings, published in Science, reveal how the enteric nervous system — a chaotic network of half a billion nerve cells and many more supporting cells inside the gut wall — is formed during mouse development. The research was led by the Francis Crick Institute, in collaboration with the University of Leuven, Stanford University, the Hubrecht Institute and the Quadram Institute Bioscience. The work was funded by the Francis Crick Institute, the Medical Research Council and the UK Biotechnology and Biological Sciences Research Council. Often known as the ‘second brain’ for its vast number of 8) ___ and complex connectivity, the enteric nervous system has a crucial role in maintaining a healthy gut. Therefore, understanding how this neural mosaic is organized could help scientists find treatments for common gastrointestinal disorders. During development, a unique and dynamic population of cells known as progenitor cells divide to produce copies of themselves, which can then generate many other types of cells. Using genetic tools, the study labelled individual progenitor cells of the enteric nervous system with unique colors and followed their descendants — also marked with the same color — through development and into the adult animal. By examining the type of cells produced by single progenitors, they could understand their properties. Results showed that some progenitors only produced nerve cells, others only produced nerve-supporting cells called glia, and some produced both. Neurons and 9) ___ originating from the same parent stayed close to each other, forming relatively tight groups of cells. Cell groups that descended from different but neighboring parent cells overlapped like a Venn diagram that could be viewed on the gut surface. Interestingly, this close relationship was maintained by the descendants of single progenitors down through all layers of the gut wall thereby forming overlapping columns of cells. The team explored whether this intricate structure of the enteric nervous system also contributes to nerve cell activity in the gut. According to the authors, a subtle electrical stimulation to the enteric nervous system showed that nerve cells generated by the same parent cell responded in synchrony, and that this suggested that developmental relationships between cells of the enteric nervous system of mammals are fundamental for the neural regulation of gut function. The authors added that now that there is a better understanding of how the enteric nervous system is built and works, it is possible to start looking at what happens when things go wrong particularly during the critical stages of embryo development or early life. Perhaps mistakes in the blueprint used to build the neural networks of the gut are the basis of common gastrointestinal problems. Recent research indicates a possible connection between early gut flora and 10) ___.


Sources: The Francis Crick Institute: Researchers: Reena Lasrado, Werend Boesmans, Jens Kleinjung, Carmen Pin, Donald Bell, Leena Bhaw, Sarah McCallum, Hui Zong, Liqun Luo, Hans Clevers, Pieter Vanden Berghe, Vassilis Pachnis. Lineage-dependent spatial and functional organization of the mammalian enteric nervous system. Science, 2017; 356 (6339): 722; ScienceDaily.com; Wikipedia


ANSWERS: 1) canal; 2) nerve; 3) motor; 4) serotonin; 5) enteric nervous systems; 6) stress; 7) flora; 8) neurons; 9) glia; 10) autism



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