Neuropod cell

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This is a 3D reconstruction of a neuropod cell utilizing a serial block face scanning electron microscopy (SBEM) data set in Imaris software. On the left side of the cell has microvilli extending into the gut lumen and the right side has a neuropod extending into the basal lamina propria. Celula L Estructura.png
This is a 3D reconstruction of a neuropod cell utilizing a serial block face scanning electron microscopy (SBEM) data set in Imaris software. On the left side of the cell has microvilli extending into the gut lumen and the right side has a neuropod extending into the basal lamina propria.

A neuropod cell is a specialized enteroendocrine cell (i.e., sensory epithelial cell) within the gut that is capable of synapsing with afferent nerves. [2] [3] Previously, transmission of sensory signals from enteroendocrine cells were thought to only occur in a paracrine fashion, in which secreted peptide hormones diffused through the lamina propria and contacted either intrinsic or extrinsic neurons, entered the circulation, and/or acted on specific target tissues. [4] [5] However, neuropod cells, discovered by Dr. Diego V. Bohórquez in 2015 and later coined in 2018, were observed forming synaptic connections with nerves in the mucosa of the small and large intestine of rodents. [3] [6] These synapses were revealed to involve neurons originating from the dorsal root ganglia and the vagal nodose ganglia of the spinal cord, which suggested that sensory information from the gut lumen could be conveyed to the brain within milliseconds of activation. [6] Also, it was found that these neuropod cells contained both pre- and postsynaptic proteins, suggesting that information could not only be conveyed to, but also received by neurons. [3] [6] [7] This newly found transmission mechanism of luminal senses from the gut to the brain may spark a new area of exploration within the gut-brain axis and sensory neurobiology.

Contents

Nutrient sensing and behavior

Although it has been understood for some time that there is a relationship between consumed food, cravings, and bodily health, it is only of recent that the mechanisms underlying gut sensation of food have been discovered. Integral to this sensation of nutrients and the regulation of postprandial physiology are enteroendocrine cells. [8] These cells are not only able to assess nutrient content of ingested food by sensing glucose, fatty acids, amino acids, monoacylglycerols, and oligopeptides, but they may also drive appetitive decisions. [8] [9] Although sugar and artificial sweeteners generate a sweet taste, natural sugar is preferred and can even be distinguished from artificial sweeteners by mice lacking taste receptors. [10] [11] [12] This suggests that the gut is important for not only discerning between the two sugars, but also guiding the animal's preference for the natural sugar over the artificial sweetener. Upon infusion of natural sugar or artificial sweetener into the small intestine, duodenal neuropod cells transduced luminal information onto distinct vagal nodose neuron populations either through glutamatergic neurotransmission (sucrose) or purinergic neurotransmission (sucralose). [9] Moreover, the animal's preference for sucrose over sucralose was abolished (90.8% to 58.9% sucrose preference) after utilizing a flexible fiberoptic cable (optogenetics) to selectively silence duodenal neuropod cells. [9] These data suggest that duodenal neuropod cells are not only capable of distinguishing natural sugar from artificial sweetener by utilizing different neurotransmitters and through activation of different neuronal populations, but they also capable of driving appetitive preferences for the natural sugar.

Microbial interactions

Gut microbiota have been known to prime the immune system and to aid in the preservation of a healthy central nervous system, which has been extensively documented in germ-free and gnotobiotic mice that present with overzealous immune systems and an abundance of neurological deficits. [13] [14] Interestingly, within these germ-free mice the general abundance of chromogranin A-positive enteroendocrine cells decreased in the ileum and increased in the colon, suggesting a potential connection between the microbiota and the normal distribution of gut sensory cells. [15] Furthermore, human and murine enteroendocrine cells possess receptors for microbe-associated molecular patterns (MAMPS) like bacterial lipopolysaccharide (LPS) and receptors for a range of bacterial metabolites like short chain fatty acids (SCFAs). [16] [17] The presence of these receptors suggest that the synaptically connected neuropod cells may be responsible for detecting microbial signals and metabolites within the gut lumen and then conveying said information to the brain. Finally, specific pathogenic bacteria (e.g., Chlamydia trachomatis ) have been implicated in the pathogenesis of irritable bowel syndrome by directly infecting enteroendocrine cells and upregulating distinct neurotransmitter transporters like glutamate. [18] [19] Also, helminth infections with Trichinella spiralis can lead to a significant reduction in food consumption, which is dependent on enteroendocrine cell presence and abundance. [20] These findings suggest that not only can pathogenic bacteria gain access to neuropod cells and possibly the associated central nervous system, but they may also be able to direct behavior of the host.

Related Research Articles

<span class="mw-page-title-main">Sensory nervous system</span> Part of the nervous system

The sensory nervous system is a part of the nervous system responsible for processing sensory information. A sensory system consists of sensory neurons, neural pathways, and parts of the brain involved in sensory perception and interoception. Commonly recognized sensory systems are those for vision, hearing, touch, taste, smell, balance and visceral sensation. Sense organs are transducers that convert data from the outer physical world to the realm of the mind where people interpret the information, creating their perception of the world around them.

<span class="mw-page-title-main">Cholecystokinin</span> Hormone of the gastrointestinal system

Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.

<span class="mw-page-title-main">Myenteric plexus</span> Part of the enteric nervous system

The myenteric plexus provides motor innervation to both layers of the muscular layer of the gut, having both parasympathetic and sympathetic input, whereas the submucous plexus provides secretomotor innervation to the mucosa nearest the lumen of the gut.

<span class="mw-page-title-main">Sensory neuron</span> Nerve cell that converts environmental stimuli into corresponding internal stimuli

Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded receptor potentials. This process is called sensory transduction. The cell bodies of the sensory neurons are located in the dorsal ganglia of the spinal cord.

<span class="mw-page-title-main">Neurotrophin</span> Family of proteins

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.

Charles S. Zuker is a Chilean molecular geneticist and neurobiologist. Zuker is a Professor of Biochemistry & Molecular Biophysics and a Professor of Neuroscience at Columbia University. He has been an Investigator of the Howard Hughes Medical Institute since 1989.

<span class="mw-page-title-main">Neuroimmune system</span>

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers, mediating neuroinflammation and wound healing in damaged neurons, and mobilizing host defenses against pathogens.

<span class="mw-page-title-main">Glucagon-like peptide-1</span> Gastrointestinal peptide hormone Involved in glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

A topographic map is the ordered projection of a sensory surface, like the retina or the skin, or an effector system, like the musculature, to one or more structures of the central nervous system. Topographic maps can be found in all sensory systems and in many motor systems.

<span class="mw-page-title-main">Enteroendocrine cell</span> Cell that produces gastrointestinal hormones

Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.

<span class="mw-page-title-main">Taste receptor</span> Type of cellular receptor that facilitates taste

A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered "sapid".

<span class="mw-page-title-main">Free fatty acid receptor 1</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 1 (FFAR1), also known as G-protein coupled receptor 40 (GPR40), is a rhodopsin-like G-protein coupled receptor that is coded by the FFAR1 gene. This gene is located on the short arm of chromosome 19 at position 13.12. G protein-coupled receptors reside on their parent cells' surface membranes, bind any one of the specific set of ligands that they recognize, and thereby are activated to trigger certain responses in their parent cells. FFAR1 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes at least three other FFARs viz., FFAR2, FFAR3, and FFAR4. FFARs bind and thereby are activated by certain fatty acids.

<span class="mw-page-title-main">Free fatty acid receptor 2</span> Protein-coding gene in the species Homo sapiens

Free fatty acid receptor 2 (FFAR2), also termed G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor. It is coded by the FFAR2 gene. In humans, the FFAR2 gene is located on the long arm of chromosome 19 at position 13.12. Like other GPCRs, FFAR2s reside on the surface membrane of cells and when bond to one of their activating ligands regulate the function of their parent cells. FFAR2 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes three other receptors which, like FFAR2, are activated by certain fatty acids: FFAR1, FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids whereas FFAR1 and FFAR4 are activated by long-chain fatty acids.

<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins, and peptides.

<span class="mw-page-title-main">Gustatory nucleus</span> Rostral part of the solitary nucleus located in the medulla

The gustatory nucleus is the rostral part of the solitary nucleus located in the medulla. The gustatory nucleus is associated with the sense of taste and has two sections, the rostral and lateral regions. A close association between the gustatory nucleus and visceral information exists for this function in the gustatory system, assisting in homeostasis - via the identification of food that might be possibly poisonous or harmful for the body. There are many gustatory nuclei in the brain stem. Each of these nuclei corresponds to three cranial nerves, the facial nerve (VII), the glossopharyngeal nerve (IX), and the vagus nerve (X) and GABA is the primary inhibitory neurotransmitter involved in its functionality. All visceral afferents in the vagus and glossopharyngeal nerves first arrive in the nucleus of the solitary tract and information from the gustatory system can then be relayed to the thalamus and cortex.

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<span class="mw-page-title-main">Taste</span> Sense of chemicals on the tongue

The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception stimulated when a substance in the mouth reacts chemically with taste receptor cells located on taste buds in the oral cavity, mostly on the tongue. Taste, along with the sense of smell and trigeminal nerve stimulation, determines flavors of food and other substances. Humans have taste receptors on taste buds and other areas, including the upper surface of the tongue and the epiglottis. The gustatory cortex is responsible for the perception of taste.

<span class="mw-page-title-main">Gut–brain axis</span> Biochemical signaling between the gastrointestinal tract and the central nervous system

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The "microbiota–gut–brain axis" includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

Sugar preference is a biological phenomena where sugar is favored over artificial sweeteners by both humans and animals.

Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, affects 1% of people over 60 years of age. In the past three decades, the number of PD cases has doubled globally from 2.5 million in 1990 to 6.1 million in 2016. As of 2022, there are ~10 million PD cases globally. In the United States, the estimated prevalence of PD by 2030 is estimated will be ~1.24 million. These numbers are expected to increase as life expectancy and the age of the general population increase. PD is considered to be a multisystem and multifactorial disease, where many factors, such as the environment, gut, lifestyle and genetics, play a significant role in the onset and progression of the disease.

References

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