ENTERIC NERVOUS SYSTEM A REVIEW - PDF document

31 ENTERIC NERVOUS SYSTEM: A REVIEW Cansu Kurt, Defne Flora Göy, Gülah Özden, Öykü Barutçu, Cüneyt BozerTrakya Unversty Faculty of Medcne, Edrne, TURKEYDepartment of Anatomy, Trakya Unversty Faculty of Medcne, Edrne, TURKEYABSTRACT En dgestve system. However, alongsde ts dgestve functons, enterc nervous system has also ganed mportance because of the dscovery of ts bdrectonal lnk wth ntestnal ora, whch has recently started to be consdered as a separate organ n addcton to ts dgestve functons. Enterc nervous system contans approxmately 100 mllon nerve cells, operates both ndependently and n coordnaton wth the central nervous system, nteracts wth many neurotransmtters and s related to many condtons and structures such as the ntestnal ora, mood, mmune sys terc nervous system (ENS) s known for ts terc nervous system conssts of neurons em bedded n the ntestnal wall. Asde from ther other functons, these neurons enable us to sense envronmental dangers and determne our reactons. For example, e enterc nervous system orgnates from the vagal segment of the neural crest, whch mgrates to the proxmal part of the gut and later spreads throughout the whole dgestve system n dstal drecton (5). or ths reason, ENS can be consdered as an al tered part of central nervous system. s system enables the communcaton formed by the sympathetc and pa e regon of the central nervous system assoc ated wth the enterc neurons s known as the autonomc Adress for Correspondence: Cansu Kurt, Trakya Unversty Faculty of Medcne, Edrne, Turkey - e-mal: cansu.kurt.dr@gmal.com Receved: 20.12.2014 - Accepted: 20.01.2015 32 neural network (4). Neuronal cell bodes n the ENS are assocated wth neural branches of two man plexuses named myenterc (Auerbach’s) plexus (MP) and submu - cosal (Messner’s) plexus (SP). MP spreads throughout the whole ntestne, runnng between the longtudnal and crcular muscle layers and bascally provdes these two muscle layers wth motor and mucosa wth secreto - motor nnervaton. MP also runs to gallbladder, to the submucosal ganglons of pancreas and to enterc gang - lons. Besdes, many mportant collaterals of myenterc neurons extend to sympathetc ganglons (5). Asde from the ablty of ENS to functon nde - pendently, t s thought that CNS plays an mportant role n the coordnaton of varous functons of ENS (1). e tght connecton of ENS wth CNS, formed by both mo - tor and sensory pathways of sympathetc and parasym - pathetc nervous system can be demonstrated as a proof for ths (4). Asde from the nuence of the CNS, there are 4 man objectves of the ENS: Smooth cells whch are responsble of the motlty of the dgestve system, Secretory cells of the mucosa, Endocrne cells of the dgestve system, Immunomodulatory and nammatory cells that man - tan the mucosal blood ow durng ntestnal secreton and generate mcrocrculaton of the dgestve system and mucosal mmunologcal, allergcal and namma - tory responses (5). ENTERIC NERVOUS SYSTEM AND IT’S INTER - CONNECTED STRUCTURES Whle enterc nervous system carres out ts fun - ctons, t nuences and s nuenced by several struc - tures. Whch structures are closely assocated wth the enterc nervous system? Fgure 1: Structures assocated wth the enterc system Fgure 1.ere are many factors assocated wth the en - terc nervous system apar

t from those mentoned abo - ve, however there are four man topcs that we want to emphasze. ese are, frst and foremost, the ntestnal ora, then mmunty and mood. Some of these regulate the functon of enterc nervous system drectly and some ndrectly. ese factors are assocated not only wth the enterc nervous system, but also wth each other. Shown above are the enterc nervous system and ther nterac - tons. If we focus on these factors separately: 1.INTESTINAL FLORA e bowels have a surface area of 400-500 m2 and consttute one of the most dense and complex ecosystems n the vertebrates. It contans all knds of sy - mboss, frst and foremost mutualsm, commensalsm and parastsm. More than 500 speces of bactera wth a number varyng between 1014 - 1015 s found n ths envronment, whch s rch of nutrents and has a stable temperature (6). Most of these bactera are found n the colon and they make the colon metabolcally most actve organ n the body. 60% of feces consst of these bactera. More than 99% of bactera n the ntestnes are anaerobc, but anaerobc bactera are more common n the cecum (7, 8). Fgure 2: Bactera dspersal n the dgestve system. Fgure 2. e densty of bactera ncreases from the stomach and the duodenum to leum+jejunum. In the colon t reaches a cellular densty much more than all known ecosystems. Most common aerobc and anaerobc bactera speces are enlsted (7).Intestnal Flora, Our Nervous System and Our Mood In some studes, the ntestnal ora s consdered as another organ. e vegetatve nervous system formed by the ora n ths regon has a role n multple aspects, such as our momentary emotonal status and t drects our eatng and drnkng habts. Studes show the mportance of the ntestnal ora n the gut-bran connecton. It s dscovered that, snce the nfancy stage, there s a constant communcaton between the bactera n our gut and our bran. s communcaton s nvolved n shapng the crcuts of the bran. It has eects on anxety and memory, creates changes n our fear center -the amygdala- and n the hppocampus, whch s found n the depths of the bran (9). nother study about ths subject s beng condu cted n Ireland on a lactobacllus stran. Lactobacllus s a harmless speces of bactera found n the ntestnes and t s one of the man components of fermented food. Researchers have found that lactobacll alters the producton of gamma-Amnobutyrc acd (GABA) receptors, an mportant neurotransmtter found n the bran cells of mce and correspondngly. ese fndngs suggest that probotc bactera could somehow have an eect on our bran (9).Intestnal Flora and Our Immune System e eects of ora on our mmune system are very mportant from the aspect that t makes the connecton between dseases and the functonng of our gut. It s a fact that cannot be gnored that due to the damagng of our ntestnal ora, resultng from the long-term and uncontrolled use of antbotcs, susceptblty to many dseases ncreases, the recovery tme s longer and other problems add on the present dsease. ntestnal bactera form a natural defense barrer and they have many protectve, structural and metabolc eects on the ntestnal epthelum. Eects of the ora on the physology of the ntestnes are shown by comparatve studes conducted on sterlzed and colonzed anmals. Eects mentone

d below are observed n anmalsey became more susceptble to nfectons,er vascularzaton s decreased,Actvty of dgestve enzymes s decreased,nnng on the walls of ntestnal muscles s observed,Producton of cytoknes and serum mmunoglobulnlevels are decreased,e numbers of Peyer’s Patches and ntraepthelal lymphocytes decrease, whereas the enterochroman cell area s wdened. Enterochroman cells are a type of gastrc ntestnal mucosa cells that produces and stores several autacods lke serotonn and prostaglandns. Most mportant reason for the prolferaton of ths cell s that the carcnod tumors of the stomach orgnate from enterochroman-lke cells (7, 10). e ntestnal ora also prevents allergens and an overreacton of the body to harmless allergens. Our ora starts to shape our mmune system startng from the nfancy (8).2.DIET In a healthy person, bactera n the ntestnal ora play an mportant role n the degradaton of protens, carbohydrates and fats found the nutrents we take n our bodes to ther buldng blocks: amno acds, monosacchardes and fatty acds. If we had no ntestnal ora, a porton of the carbohydrates we take nto our body would not be dgested and utlzed. Bactera transform the carbohydrates they ferment nto short-chan fatty acds and these fatty acds ncrease the water absorpton capacty of the ntestnes, decrease the number of harmful bactera, help the absorpton of mnerals (especally magnesum, ron and calcum) n the body. ese bactera produce vtamn K and enable ts absorpton (8). n addton to all these, det has mportant eects on the ntestnal ora, too. Correct nutrton s necessary for the health of the ntestnal ora, the replacement of mcroorgansms s managed by correct nutrton. Probotcs modfy the balance between the benefcal and harmful bactera n favor of the benefcal bactera and functonng of ntestnal cells (8). robotc bactera used as support s usually pro vded from fermented products such as yoghurt, cheese, pckles, beer, wne, kefr and kums. A low-sugar and low our det, rch n food such as fruts, vegetables, meat and eggs, also strengthen the ntestnal ora (8). 34 robotcs are carbohydrates that ncrease the actvty of non-pathogenc bactera, manage ther cooperaton and that humans cannot dgest drectly. A shorter descrpton would be: Probotcs are the nutrents of probotc bactera. Legume, onon, garlc, banana and leek are mportant sources of probotcs. Breast mlk s also owng to ts olgosaccharde-rch ngredents (8). ollowng the b-drectonal connecton between the ntestnal ora and nutrton, we should also menton the eect of enterc nervous system on our eatng habts. Accordng to the fndngs of Belgan researchers (9), n fact, certan ngredents of nutrents aect the hormones that send sgnals to the bran va the enterc nervous system and ths contrbutes to the formaton of taste sensaton. Studes on mce show that, under stress, mce prefer fatty food (namely, hgh-energy food) and that ths s related to the producton of the hormone “ghreln”, whch trggers hunger n the bran, by the enterc nervous system. Researchers have determned that mce wthout ghreln receptors n ther brans do not prefer fatty food under stress. Ghrel

0;n s only one of the many neurotransmtters that connects enterc nervous system and the bran and enables the lnks between mood and 3.ENTERIC NERVOUS SYSTEM ANDIMMUNITY ENS has varous functons. It s responsble from controllng motlty, endocrne and exocrne secretons and the mcrocrculaton of the dgestve system and also plays an mportant role n the control of mmunoregulatory nammatory processes and t s as well as responsble of the control of the motlty, exocrne and endocrne secretons and macrocrculaton of the dgestve system. erves whch form the enterc nervous system are under the eect of the autonomous nervous system. Enterc nervous system conssts of approxmately 100 mllon neurons and creates a consderably systematc neural network n the gut. s neural network formed by the bran and the enterc nervous system s called the gut-bran axs. Wth ts lnks to mmunty and endocrne mechansms, ths neural network nuences ntestnal homeostass (11). nglons consst of nteractve nerve cells, ter mnal branches formed by nerve fbers and glal cells. Glal cells are components of the ENS and resemble the astrocytes n the CNS. Cells called enterochroman cells that are responsble of the producton of serotonn and prostaglandns n the gastrc ntestnal mucosa nterleukns (cytoknes that allow the communcaton between leukocytes) and the response generated by the cytoknes dsplays MHC-II antgens. s stuaton shows that enterc gla cells and therefore the ENS has a role n the generaton of nammatory response n the ntestne (12). lceratve colts and Crohn’s dsease are nf lammatory bowel dseases, whch have no connectons wth known agents such as nfecton, drugs, schema and radaton (13). It s suggested that there are many underlyng factors that cause nammatory bowel dseases. Asde from envronmental factors; genetcs, mmunty and some nfectous reasons are to count among these. In recent years, there s an ncreasng number of evdence suggestng that nammatory cells and mmune system have a complex nteracton wth the enterc nervous system. s complex nteracton can be explaned lke ths: Intestnes are densely nnervated wth autonomous nerve fbers and autonomous nerves are n close connecton wth mmune respondng cells n the ntestnes. Stmulaton of sensory nerves regulates nammaton on mmune respondng cells through the neuropeptdes. Alteratons of nerve fbers are observed n both ulceratve colts and Crohn’s dsease. Studes demonstrate that topcal applcaton of ldocane prevents neural transmsson and; accordngly, reducton of mucosal nammaton could be possble (14, 15). everal alteratons referred to as neuromatous changes are observed n nammatory bowel dseases. ese are percepton of mpulses, motlty and alteratons n secreton. Besdes, hypertrophy n submucosal and myenterc nerve plexuses, excessve ncrease n the number of cells and structural defects (16).4.CONNECTION BETWEEN MOODAND ENTERIC NERVOUS SYSTEM Dsorders on every level n bran-gut communcaton and autonomc functon dsorders play an mportant role n the geness of recurrent abdomnal pan (RAP) (2, 3). Recurrent abdomnal pan s one of the most common problems n chldren. Has a reported prevalence of 10-20% n chldhood age group. RAP s not a dagnoss; t s

only a defnton, a symptom. Several dseases can cause ths clncal appearance. Organc reasons as well as several psychologcal problems assocated wth our emotonal world could be underlyng these dseases (2, 3, 17). 35 ntl 1980s, RAP was consdered as a psycho logcal condton, f no organc cause could be detected. In later years, ndvdual derences and contrbutng factors to these derences came nto promnence, whereas recently bologcal, physologcal and socal factors are addressed. Studes n recent years pont out that underlyng etology of RAP s related to the enterc nervous system, whch s accepted as the second bran, bran-gut relatons, motlty dsorders of the dgestve system and especally vsceral hypersenstvty (18). s hypersenstvty could be caused by an nfecton, trauma or nflammaton, whereas stress and several psychologcal factors are also thought to play a role n the ENS becomng overly exctable (3, 19).5.ENTERIC NERVOUS SYSTEM AND NEUROTRANSMITTERS More than twenty types of neurotransmtters are found n the neurons of the enterc nervous system. Latest studes reported that ths number has reached forty and functons of most these neurotransmtters are dscovered. e presence of acetylcholne and serotonn, gamma-Amnobutyrc acd (GABA), adenosne trphosphate (ATP), vasoactve ntestnal polypeptde (VIP) and ntrc oxde (NO) s shown. Numerous ENS neurons contan multple neurotransmtters and alternatve bndngs of medators accordng to the locaton of the neurons create alternatve functons. Most of the neurons wth dstnctve functons can use the same neurotransmtters. Neurotransmtters are spread around the myenterc and submucous plexuses (5, 9). otln, somatostatn, proknetc agents and opates ntate mgratng motor complex actvty. Tonc nhbton of motlty and relaxaton of sphncters are enabled by neurons contanng VIP and NO. A cause of achalasa dsorder s the malfuncton of nhbtory neurons of the myenterc plexus of oesophagus, contanng VIP and NO (5). NO and VIP are the two man neurotransmtters that help non-adrenergc, non-cholnergc nerves to relax the smooth muscle cell. e connecton between these two molecules s stll a matter of debate and there are studes ndcatng that NO and VIP are cotransmtters and are smultaneously released from enterc nhbtory nerves (20). mong the neurotransmtters of the enterc ner vous system, serotonn (5-HT, 5-hydroxytrptamne) has gradually ganed mportance. Serotonn s released from the enterochroman cells. 5-HT3 and 5-HT4, whch are 5-HT receptors, control gastrontestnal sensaton, motlty and secretons (21). Serotonergc receptors are lnked to depresson, food ntake and obesty, bpolar dsorders, obsessve compulsve and anxety dsorders, sleep, analgesa, nausea and vomtng, drug addctons. An ncrease n the serotonn level n synapses decreases food ntake and prevents obesty and sleep dsorders lke nsomna, elmnates the depresson seen aer the wthdrawal from an addcton. Selectve serotonn reuptake nhbtors (SSRI), monoamne oxdase (MAO) nhbtors that degrade excessve serotonn n the cell body, tryptophan and hydroxytryptophan supplements are used (22). e combned use of some of these drugs ncreases the serotonn level and leads to the clncal condton known as the serotonn sy

ndrome (fever, darrhea, changes n mental state, myoclonus, agtaton, tremor, ncrease n reexes) (23). 95 percent of the body’s serotonn producton s found n the ntestnes. Selectve serotonn reuptake nhbtors, antdepressant drug treatments known as SSRIs rases serotonn levels. It s an expected condton that the sde eects of drug treatments, whch cause chemcal alteratons n the bran, are dgestve complants. A drug that prevents the release of serotonn from the ntestnes s shown to prevent postmenopausal osteopoross n rodents. Serotonn released from the second bran could play a role n autsm, whch s the earlest recognzable developmental dsorder n the early chldhood (1, 9). eurotransmtter-ENS connecton showed that regulatng the levels of released neurotransmtters could treat many dseases. ere are data that suggests that acupuncture ntates norepnephrne, serotonn and dopamne release. In 1977, researchers showed the frst attempt to use acupuncture method to evaluate patents wth psychosomatc symptoms and under drug therapy. Partcpants experenced a reducton n tenson, restlessness, sadness, headache, cephalc paresthesa and loss of appette durng the study. e authors vewed acupuncture as a safe and potentally eectve method of treatng depresson (24). esearchers have studed the eect of electroacu puncture on levels of neuropeptde Y (NPY) over 4 weeks n a small plot study of sx patents wth major depresson. Durng acupuncture therapy, NPY plasma levels decreased n fve patents. s fndng was assocated wth clncal mprovement of depresson. Acupuncture allows the release of serotonn and other neurotransmtters and therefore s a practce that deserves further research n the treatment of depresson as an alternatve for antdepressants, whch have numerous sde eects (24). 36 CONCLUSION Enterc nervous system s a system wth many regulatory features such as the ntestnal ora, our mood and our det. ey are n tght connecton wth neurot - ransmtters whle carryng out these functons. Enterc nervous system s a neural structure that especally through the aerent and eerent fbers n the vagus nerve, the neurotransmtters t releases and ts connectons wth the autonomous nervous system. As a consequence of these tght connectons, any condton that aects our ntestnes can also show ts eect on the central nervous system. Lkewse, a problem n our n - testnes can reach our central nervous system and aect our mood. It s shown that the our enterc nervous system deserves more attenton wth ts hundred mllon nerves (whch s the second hghest number aer the bran), ts nuences on our central nervous system and the results that emerge wth the help of our CNS. Ethcs Commttee Approval: Not applcable. Informed Consent: Not applcable. Conct of Interest: e authors declared no conct of n - terest. Fnancal Dsclosure: e authors declared that ths study receved no fnancal support. REFERENCES 1.Hadhazy A. nkTwce: How eGut’s ’Second Bra - n’ InuencesMoodandWellBeng. http://www.scent - fcamercan.com/artcle/gut-second-bran/ (20 January 2015). 2.Mahajan L, Wylle R. Chroncabdomnalpan of chl - dhoodandadolescence. In: Wylle R, Hyams JS (eds), PedatrcGastrontestnalDsease, Pathophysology, D - agnoss, Management, 2nd edton 1999; 3-13. 3. Zeter DK, H

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