Abstract
The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to identifying various neuronal cytotypes belonging to ENS in baseline conditions. The second part of the study provides evidence on how these very same neurons are altered during Parkinson’s disease. In fact, although being defined as a movement disorder, Parkinson’s disease features a number of degenerative alterations, which often anticipate motor symptoms. Among these, the GI tract is often involved, and for this reason, it is important to assess its normal and pathological structure. A deeper knowledge of the ENS is expected to improve the understanding of diagnosis and treatment of Parkinson’s disease.
Highlights
The gastrointestinal (GI) tract is a long tubular structure whose wall is deputed to important and complex functions in terms of motor activity, absorption, and secretion
A historical background was provided from the recognition of an autonomous nervous network in the GI tract up to the employment of a vast number of classification methods based on different criteria, leading to the identification of several cytotypes; (2) The second part focuses the attention on the enteric nervous system (ENS) cell population to examine which cytotypes are involved in Parkinson’s disease
It is ascertained that the complex network of the ENS includes several cell types
Summary
The gastrointestinal (GI) tract is a long tubular structure whose wall is deputed to important and complex functions in terms of motor activity, absorption, and secretion. The ENS derives from pre-enteric vagal (hindbrain) as well as sacral neural crest cells and includes efferent and afferent neurons and interneurons, making this system capable of carrying reflexes in the absence of inputs from the central nervous system (CNS) This network is relatively independent of the classic sympathetic and parasympathetic innervations, allowing the onset of modulated local responses [1,2,3]. According to the classic Braak’s hypothesis [9], neurodegenerative diseases, in particular Parkinson’s disease, can recognize a peripheral origin when putative pathogens enter the mucosa of the GI tract, inducing misfolding and aggregation of the hallmark of this pathology, α-synuclein, in specific neuron subtypes of the ENS, and spreading retrogradely to CNS via vagal preganglionic fibers, up to the dorsal motor nucleus of this nerve and other central nervous structures [10,11,12,13,14]. FiFgiugruere1.1M. iMcriocbroiobtiao–tgau–gt–ubtr–abirnaainxias.xTisw. oTwsuobtsyupbetsypofesPaorfkPinasroknin’ssodnis’seadsiesepaasteienptastiheanvtse hbaeevne rbeece-n ogrenciozgedni:zaedb:raainb-rfaiirns-tfi(rtostp(-tdoopw-dno)wtynp) ety, pweh, werheetrheethhealhlmalalmrkarokf othf itshpisapthaothloogloyg(yα(-αsy-snyunculeclieni)ni)niintiiatilalylly apappepaerasrsinintthhee bbrraaiinn wwiitthhsseeccoonnddaaryryspspreraedaidnigngtottohethpeerpiperhieprhaelraaultoaunotomniocmniecrvnoeursvosyusstesmys;taembo; daybofidrsyt-(fbirosttto(bmo-tutopm) t-yuppe),twyphee,rewthheerpeatthheoploagtyhoolroiggiynoatreigsiinnatthees einnttehreiceonrtepreicriporheprearlipauhteornaol mauictonneormvoicus nroesdyrvestogeuemns easrynasdttivethmeednainsspedaresthaedse,nsstusopctrhheeaabds rsPatianor.ktIihnnestohbnirsa’scinad.sieIsn,eaatcshceio,srcdcaainnsger,etoacocBcgronariadzkie’nsaghpytoeproBitprhaheaeskrisa’s,l nhoeyruipgroointdhewegsheisne,nenrapetuuiv-- e tadtiivseeaspeast,hsougcehnassePnatrekrinthsoen’ms udcisoesaaseo,fcatnhereGcoIgntriazcet,a ipnedruipchinegralmoirsifgoilndiwngheannpdutaagtigvreegpaattihoongeonf s αe-snytneructhleeinmiunctohseaEoNf tSh,eanGdI tfrinacatl,lyinsdpurecaindginmg irseftorlodginragdaenlydtaogCgNreSgavtiiaonvaogfaαl -psyrenguacnlegilnioinnicthfiebEerNs,S, upantdo fithnealdlyorssparlemadoitnogr rneutrcolegurasdoeflythtios CneNrvSevaiandvafginaal lplyreogtahnegrlicoennitcrafilbneerrsv, ouupstostrtuhcetudroerss.aAl mportio- r on-ulickleums oefchthainsinsmervheaasnadlsfionablelyenotphreorpcoensetrdalfnorermvoiusfsosldtreudctupreost.eiAnsprpioronp-laikgeatmioenc,haanndismdihffaesreanlsto robueteens phraovpeobseedenfohrympiostfhoeldsiezdedprtooteaicncsopurnotpfaograthioisn,caenlld-tod-icfefellresnptrreoaudtiensgh, ainvcelubdeeinnghvyapgoathl e(1si)zaenddto noancc-vouagnatlf(oirmtmhius nceelal-ntod-cceirlclusplarteoardyisnygs,tienmclsu)d(2in) gpavtahgwaal y(1s). and non-vagal (immune and circulatory systems) (2) pathways
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