Daphnia longicephala neuropeptides: Morphological description of crustacean cardioactive peptide (CCAP) and periviscerokinins in the Ctenodaphnia central nervous system

The publication of the Daphnia genome has driven research in this ecologically relevant model organism in many directions. However, information on this organism’s physiology and the relevant controlling factors is limited. In this regard, especially neuropeptides are important biochemical regulators that control a variety of cellular processes, which in combination influence physiological conditions and allow the adaptation of the internal physiological state to external conditions. Thus, neuropeptides are prime in understanding an organism’s physiology. We here aimed to detect and describe the distribution of evolutionary conserved neuropeptides including the crustacean cardioactive peptide (CCAP) and peptides of the family periviscerokinins (PVKs) in the central nervous system and the periphery of the Daphnia longicephala head region. We were able to identify a large pair of CCAP immunoreactive cells within central nervous system. In addition, in the periphery we found CCAP immunoreactive cells in the epidermis of the head with processes indicating cuticular secretion. Furthermore, we were able to identify and describe a complex neuronal circuit of PVK neuropeptides in the central nervous system. The data obtained in this study will provide important background information for future investigations aiming to unravel the cellular, neuronal and physiological pathways in a highly adaptive organism such as Daphnia.     

The distribution of bovine pancreatic polypeptide/FMRFamide-like immunoreactivity in the ventral nervous system of the locust

The distribution of bovine pancreatic polypeptide (BPP) FMRFamide-like immunoreactivity is described in the ganglia of the ventral nerve cord and in the peripheral median nervous system of the locust, Schistocerca gregaria. Immunoreactive cell bodies occur in three regions of the thoracic ganglia: 1) two pairs of cells lie in the anterior of the ganglion ventral to the root of nerve 1 and the anterior ventral association centre; 2) a group of cells lies in the ventral midline at the level at which nerves 3 and 4 leave the ganglion; 3) and two bilaterally symmetrical, posterior lateral groups lie between nerves 5 and 6 at the edge of the ganglion. Immunoreactive cell bodies in the suboesophageal and abdominal ganglia are confined to the midline and are distributed along the anterior-posterior axis both dorsally and ventrally. The processes of the posterior lateral groups have been traced into the neurohaemal organs of the median nerve and beyond. In the periphery such processes innervate the salivary glands and various muscles. The nature of the endogenous antigen contained in the immunoreactive cells has been investigated with the use of antisera against other peptides of the pancreatic polypeptide family, namely avian pancreatic polypeptide, neuropeptide Y, and peptide YY. In addition, BPP antisera not specific for the C terminal hexapeptide have been tested. Liquid preabsorption experiments with BPP and FMRFamide (the molluscan cardioacceleratory peptide) suggest that the endogenous peptide antigen contained in the stained neurones may belong to the pancreatic polypeptide family or to the FMRFamide family.     

Peptidergic modulation of a neuromuscular junction inAplysia: bioactivity and immunocytochemistry

Three endogenous peptides were assayed for bioactivity at an Aplysia neuromuscular junction. Evoked contractions were enhanced by Phe-Met-Arg-Phe-NH2 (FMRFamide) and suppressed by arginine vasotocin; small cardioactive peptide B (SCPB) also enhanced contractions at low concentrations, but caused suppression at higher doses. In accordance with their putative roles as neuromodulators, immunocytochemistry revealed FMRFamide-like and SCPB-like fibers on the muscle surface.     

Discovery and functional study of a novel crustacean tachykinin neuropeptide

Tachykinin-related peptide (TRP) refers to a large and structurally diverse family of neuropeptides found in vertebrate and invertebrate nervous systems. These peptides have various important physiological functions, from regulating stress in mammals to exciting the pyloric (food filtering) rhythm in the stomatogastric nervous system (STNS) of decapod crustaceans. Here, a novel TRP, which we named CalsTRP (Callinectes sapidus TRP), YPSGFLGMRamide (m/z 1026.52), was identified and de novo sequenced using a multifaceted mass spectrometry-based platform in both the central nervous system (CNS) and STNS of C. sapidus. We also found, using isotopic formaldehyde labeling, that CalsTRP in the C. sapidus brain and commissural ganglion (CoG) was up-regulated after food-intake, suggesting that TRPs in the CNS and STNS are involved in regulating feeding in Callinectes. Using imaging mass spectrometry, we determined that the previously identified CabTRP Ia (APSGFLGMRamide) and CalsTRP were co-localized in the C. sapidus brain. Lastly, our electrophysiological studies show that bath-applied CalsTRP and CabTRP Ia each activates the pyloric and gastric mill rhythms in C. sapidus, as shown previously for pyloric rhythm activation by CabTRP Ia in the crab Cancer borealis. In summary, the newly identified CalsTRP joins CabTRP Ia as a TRP family member in the decapod crustacean nervous system, whose actions include regulating feeding behavior.     

Neuropeptides in insect sensory neurones: tachykinin-, FMRFamide- and allatotropin-related peptides in terminals of locust thoracic sensory afferents

Sensory afferents in the thoracic ganglia of the locust Locusta migratoria were labelled with antisera to different neuropeptides: locustatachykinins, FMRFamide and allatotropin. The locustatachykinin-immunoreactive (LTKIR) sensory fibres were derived from the legs and entered the ventral sensory neuropil of each of the thoracic ganglia via nerve 5. In the thoracic neuropil, the LTKIR sensory fibres formed a distinct plexus of terminations ventrally in the ipsilateral hemisphere. The peripheral cell bodies of the sensory neurones could not be revealed, but lesion experiments indicated that origin of the LTKIR fibres was the tarsus of each leg. Possibly the thin fibres are from tarsal chemoreceptors. Double labelling immunocytochemistry revealed that all the LTKIR sensory fibres contained colocalized FMRFamide immunoreactivity. A larger population of sensory fibres reacted with antiserum to moth (Manduca sexta) allatotropin. By means of double labelling immunocytochemistry, we could show that the LTKIR fibres constituted a subpopulation of the larger set of allatotropin-like immunoreactive fibres. Thus some sensory fibres may contain colocalized peptides related to locustatachykinins, FMRFamide-related peptide(s) and allatotropin-like peptide. A separate non-overlapping small set of sensory fibres in nerve 5 reacted with an antiserum to serotonin. Sensory fibres of the other nerves of the ventral nerve cord, including the abdominal ganglia, did not react with the peptide antisera. Since acetylcholine is the likely primary neurotransmitter of insect sensory fibres, it is possible that the peptides and serotonin are colocalized with this transmitter and serve modulatory functions in a subset of the leg afferents.     

SCPB- and FMRFamide-like immunoreactivities in lobster neurons: Colocalization of distinct peptides or colabeling of the same peptide(s)?

Virtually all of the SCPB-like immunoreactive neurons (ca. 60 cells) in the lobster Homarus americanus also contain FMRFamide-like immunoreactivity. Control experiments reveal that SCPB-and FMRFamide-like immunoreactivities are successfully preadsorbed with their specific antigens, while the normal staining pattern is retained following preadsorption of each antibody with the alternate peptide. These experiments potentially lead to the conclusion that the anti-SCPB and anti-FMRFamide antibodies are labeling distinct compounds that are colocalized in lobster neurons. The lobster nervous system does not, however, contain authentic FMRFamide, but rather several FMRFamide-like compounds (Trimmer et al., J. Comp. Neurol. 266:16-26, 1987). The most abundant of these is the octapeptide TNRNFLRFamide. Experiments demonstrate that SCPB-like immunoreactivity is completely preadsorbed with synthetic TNRNFLRFamide, while there is a significant or complete loss of staining after preadsorption of the FMRFamide antibody with this molecule. Met-enkephalin-Arg-Phe-amide (YGGFMRFamide), an extended opioid peptide containing the FMRFamide sequence, also preadsorbs SCPB- and FMRFamide-like immunoreactivities, while Met-enkephalin-Arg-Phe (YGGFMRF) has no effect on the staining properties of these antibodies. These results suggest that the SCPB antibody can bind to extended forms of FMRFamide-like molecules, and that anti-SCPB and anti-FMRFamide antibodies may be colabeling one or more FMRFamide-like molecules in lobster neurons.     

Biological characteristics of brain natriuretic peptide and its association with central nervous system diseases

OBJECTIVE: To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide (BNP), and analyze its role in central nervous system diseases. DATA SOURCES: An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of "brain natriuretic peptide (BNP), central nervous system, subarachnoid hemorrhage (SAH), brain edema, epilepsy". Other articles were searched in China Hospital Knowledge Database (CHKD) by concrete name of journals and title of articles. STUDY SELECTION: The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION: Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS: At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without –outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION: As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.     

Biological characteristics of brain natriuretic peptide and its association with central nervous system diseases

OBJECTIVE： To explain the mechanisms of tuhe synthesis, secretion and regulation of brain natriuretic peptide （BNP）, and analyze its role in central nervous system diseases. DATA SOURCES： An online search of Pubmed was undertaken to identify articles related to BNP published in English from January 1990 to February 2007 by using the key words of ＂brain natriuretic pepfide （BNP）, central nervous system, subarachnoid hemorrhage （SAH）, brain edema, epilepsy＂. Other articles were searched in China Hospital Knowledge Database （CHKD） by concrete name of journals and title of articles. STUDY SELECTION： The collected articles were primarily screened, those about BNP and its association with central nervous system diseases were selected, whereas the obviously irrelative ones excluded, and the full-texts of the other literatures were searched manually. DATA EXTRACTION： Totally 96 articles were collected, 40 of them were enrolled, and the other 56 were excluded due to repetitive studies or reviews. DATA SYNTHESIS： At present, there are penetrating studies on BNP in the preclinical medicine and clinical medicine of cerebrovascular and cardiovascular diseases, and the investigative outcomes have been gradually applied in clinical practice, and satisfactory results have been obtained. However, the application of BNP in diagnosing and treating central nervous system diseases is still at the experimental phase without - outstanding outcomes, thus the preclinical and clinical studies should be enhanced. CONCLUSION： As a kind of central medium or modulator, BNP plays a certain role in the occurrence, development and termination of central nervous system diseases, the BNP level in serum has certain changing law in SAH, brain edema, epilepsy, etc., but the specific mechanisms are unclear.     

The involvement of the sympathetic nervous system in the centrogenic pressor and tachycardiac effects of prostaglandins E2 and F2α in anaesthetised cats

The intracerebroventricular (i.c.v.) administration of prostaglandin E₂ (PGE₂, 1 μg) and prostaglandin F_2α (PGF_2α, 10 μg) produced prolonged pressor and tachycardiac responses in chloralose-anaesthetised cats. Phenoxybenzamine-pretreatment completely prevented the pressor response without altering the tachycardiac response, whereas propranolol intervention completely inhibited the tachycardiac response and also attenuated the pressor response. The pretreatment with pentolinium completely antagonised both the pressor and tachycardiac responses to i.c.v. PGE₂ and PGF_2α. The results suggest that the centrally administered PGE₂ and PGF_2α augment sympathetic outflow to the heart and vascular system and thereby cause excitatory cardiovascular responses in anaesthetised cats.     

Distribution of NPY and NPY-Y1 receptor-like immunoreactivities in the central nervous system of Triatoma infestans (Insecta: Heteroptera)

The distributions of neuropeptide Y (NPY) -like immunoreactivity (LI) and that of its Y1 receptor (Y1), as well as their coexistence with cholecystokinin (CCK) -LI, were studied in the central nervous system of Triatoma infestans by using immunohistochemistry. NPY-immunoreactive (IR) cell bodies and fibers were observed in the brain, subesophageal ganglion, and thoracic ganglia. NPY-IR somata were seen in the optic lobe and the anteromedial and caudolateral soma rinds of the protocerebrum. Immunostained cell bodies were also found in the lateral edge of the antennal lobe glomeruli as well as in the caudal part of the antennal mechanosensory and motor center. The subesophageal ganglion harbored few NPY-IR perikarya and fibers in the three neuromeres. Positive somata of the prothoracic ganglion were detected near both the cephalic and posterior connectives as well as by the root of prothoracic nerve I, whereas in the posterior ganglion, they were seen by the roots of mesothoracic and abdominal nerves. Coexpression of NPY-LI and CCK-LI was seen in cell bodies of the protocerebrum, the subesophageal and posterior ganglia. Protocerebral Y1-IR cell groups were detected in the anterolateral and posteromedial soma rinds and at the level of the lamina ganglionaris and the external optic chiasma. Numerous positive perikarya surrounded the antennal lobe glomeruli as well as the antennal mechanosensory and motor center. Other immunostained cell bodies were seen in the posterior edge of the esophageal canal and by the roots of the mandibular and the maxillary nerves. Y1-IR cell bodies of the prothoracic ganglion were found near the roots of prothoracic nerves I-II, whereas in the posterior ganglion, they were located mainly in the abdominal neuromeres. Coexpression of Y1-LI and CCK-LI were detected in several brain areas as well as in the metathoracic and abdominal neuromeres of the posterior ganglion. When assessed by immunoblotting, Y1 antibodies detected two protein bands between 34 and 46 kDa. Analysis of the distribution patterns of NPY-LI and Y1-LI suggest that peptide and receptor are mainly involved in the processing of information coming from sensory receptors.     

1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo

We have mapped areas within the central nervous system (CNS) of the developing fetal rat which immunostain for the 1,25-dihydroxyvitamin D₃ receptor (VDR). The VDR was detected from days 12 to 21 of gestation throughout the CNS; immunostaining was particularly intense in the neuroepithelium and within the differentiating fields of various areas of the brain. Cells within the spinal cord, dorsal root, and other ganglia exhibited positive staining for the VDR. The intensity of staining for the VDR diminished or disappeared in the neuroepithelium throughout the CNS during the later days of development, while in the differentiating fields single VDR immunoreactive cells were observed. The presence of the VDR in the CNS was confirmed by in situ hybridization and RNA-based polymerase chain reaction methods with di-deoxy sequencing of the resultant DNA product. These results support the hypothesis that 1,25-dihydroxyvitamin D₃, through interactions with the VDR, may play a role in the development of the CNS.     

Immunological localization of Tritonia peptide in the central and peripheral nervous system of the terrestrial snail Helix aspersa

We report here evidence that the pedal peptides (Peps) first discovered in mollusks may be neurotransmitters with a general role in control of molluscan somatic and visceral muscles. Using Tritonia peptide (TPep) antiserum we obtained morphological evidence for such a role in Helix aspersa. We localized 1,200-1,400 small and medium-sized (5-40 microm) TPep-IR neurons in the central nervous system of Helix and demonstrated the presence of these neurons in each ganglion. Many TPep-immunoreactive (IR) neurons were motoneurons that sent axons to almost all peripheral nerves. TPep-IR fibers innervated the foot, esophagus, hermaphroditic duct, optic tentacles, salivary gland, heart, and proximal and distal aorta. In peripheral tissues TPep-IR fiber ramifications were mostly associated with muscles and with ciliated epithelia. In addition, TPep-IR fibers were in the neuropil of the ganglia, the commissures, and the connectives, and they formed axosomatic terminals in the central nervous system. TPep-IR neurons were found in the esophagus and hermaphroditic duct and as sensory receptors in the bulb of the optic tentacles. These results from Helix, and those reported elsewhere from other mollusks, suggest a general involvement of TPep-like substances in control of muscle- and ciliary-driven motor activities, including perhaps their antecedent sensory and central axosomatic integrative activity.     

ETA and ETB receptor antagonists synergistically increase extracellular endothelin-1 levels in primary rat astrocyte cultures

Astrocytes produce and bind endothelins (ETs), suggesting that these cells have ET autoregulatory and eliminatory functions. To further investigate these functions in primary rat astrocytes, ET-1 levels in the cell culture media (RIA/HPLC) and intracellular content of ET-1 mRNA (RT PCR) were measured under basal and stimulated (thrombin, 2.2 U/ml) conditions in the presence and absence of ET_A and ET_B selective antagonists (BQ123 or LU135252, and BQ788, respectively). Neither basal nor stimulated ET-1 levels in astrocyte media were influenced by ET_A or ET_B antagonists alone, but were significantly increased by a combination of both. ir ET-3 levels were not affected by antagonist treatment. Exogenous ET-1, added to the cultures, was rapidly cleared from the supernatant; this clearance was markedly inhibited by a combination of BQ123 and BQ788. ET-1 mRNA levels were not altered by any treatment. To conclude, in primary rat astrocyte cultures, extracellular ET-1 is cleared by binding to ET-receptors, apparently involving both, ET_A and ET_B sites. Thus, a blockade of the astrocytic ET eliminatory function as a consequence of the in vivo application of non-selective ET receptor antagonists may lead to increased extracellular ET levels in the brain.     

Nerve fibre degeneration of the central and peripheral nervous systems in severe protein deprivation in rats

Summary Knowledge from previous reports that kwashiorkor in man may lead to nerve fibre degeneration prompted this study on rats. The rats were subjected to severe protein deprivation from 6 weeks of age. Protein deprivation was achieved by feeding the rats ad lib with a diet containing only 1.5% protein. Control rats received an iso-caloric diet with 14% protein. The vitamin content in both diets was well above normal requirements. In relation to body weight the protein-deprived rats did not consume less food than the control rats. Protein deprivation resulted in stunted body growth, markedly reduced values of serum albumin, and changes in the fur accompanied by areas of alopecia. Furthermore, the protein-deprived rats showed degeneration of nerve fibres in the medial parts of the posterior columns of the cervical but not the sacral part of the spinal cord and nerve fibre degeneration in the distal but not the proximal parts of the longitudinal tail nerves. Teased nerve fibre preparations of the tail nerves revealed changes consistent with the Wallerian type of degeneration. It is concluded that severe protein deprivation in young rats may lead to a dying-back type of neuropathy in the central and peripheral nervous systems.     

Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: Extra and intrapancreatic ganglionar cells and telocytes in the degus

This study shows for the first time the presence of intra and extrapancreatic ganglionar neurons and telocytes in Octodon degus such as those described in human and guinea pig pancreas. Pancreatic ganglionar neurons were identified by their histological characteristics as well as their positive immunostaining with mouse anti-human neuron specific enolase (NSE) antibody. Somatostatin secreting delta cells (D cells) in the islets of Langerhans were identified by positive immunostaining with rabbit antihuman polyclonal somatostatin antibody. Electron microscopy evidenced the presence of some unmyelinated axons in the interlobular spaces or septa, usually located adjacent to blood vessels and the exocrine epithelial ducts. The presence of telocytes with at least 2 telopodes was observed in the interlobular space, frequently in close spatial relationship with blood vessels and nerve endings. Telocytes were often observed in the vicinity or even in close proximity with both secretory acini and exocrine epithelial ducts and regulatory nerves and blood vessel apparatuses. A possible framework has been put forward within which such structures might contribute to elicit physiological responses in the pancreas. Further studies of synaptic interactions within and between pancreatic neuron cells are needed to help clarify the morphological results reported here. A broad overview of the field of neurogastroenterology with focus on the pancreas of O. degus related to the enteric nervous system (ENS) is provided in order to help design future studies on the connections of specific neurons forming pancreatic pathways, their neurotransmission processes and how disruption of these pathways may contribute to pancreatic disease.     

Species differences in the distribution of central 5-HT1 binding sites: a comparative autoradiographic study between rat and guinea pig

In this study, we compared the localization of central 5-HT₁ binding sites of rat and guinea pig. The 5-HT_1B sites were absent in the guinea pig brain. Good correlations were found between species in the regional distribution of 5-HT₁ sites labelled with [³H]5-HT(r = 0.73), 5-HT_1A sites labelled with [³H]8-OH-DPAT (r = 0.87), and 5-HT_1B versus 5-HT_1D sites labelled with [³H]5-HT in the presence of ipsapirone and DOI (r = 0.76). Despite the overall similarities, species differences were observed in many brain regions. The CA1/CA2 fields of the hippocampus and the dorsal subiculum displayed significantly more 5-HT_1A receptor binding in guinea pig than in rat. Conversely, the 5-HT_1A binding in dorsolateral septum, cingulate cortex and laminae IV-V of the neocortex, was more pronounced in rat. Areas almost exclusively containing 5-HT_1B or 5-HT_1D sites, such as the ventral pallidum, globus pallidus and substantia nigra, expressed markedly more [³H]5-HT binding in rat as compared to guinea pig, while the opposite occurred in claustrum, dorsal endopiriform nucleus, lateral geniculate nucleus, and superficial grey layer of the superior colliculus. The implications of the species differences are illustrated by the binding of [³H]eltoprazine. The distribution of [³H]eltoprazine binding sites showed a good correlation with that of the 5-HT_1B sites in rat (r = 0.89), and with that of the 5-HT_1A sites in guinea pig (r = 0.97). The data give rise to the possibility that differences in the presence and distribution of 5-HT₁ receptor sites are related to species differences in behavioral, neurochemical and physiological responses to drugs with 5-HT₁ receptor affinity.     

Peptide immunoreactivity of the ciliary ganglion and its accessory cells in the rat

By means of immunohistochemistry, calcitonin gene-related peptide, Leu-enkephalin and neuropeptide Y localize to rat ciliary and accessory ganglion cells. The proportion of ciliary and accessory neurons immunoreactive to each peptide is provided and compared to previous data for vasoactive intestinal peptide. These findings indicate considerable neurochemical complexity for a parasympathetic ganglion with a small cell population.     

Involvement of GABAB receptor systems in experimental depression: baclofen but not bicuculline exacerbates helplessness in rats

There are two γ-aminobutyric acid (GABA) hypotheses of the antidepressants action: an increase in GABA_A neurotransmission or a decrease in GABA_B neurotransmission may contribute to action of antidepressants. In this study, involvement of GABA_A and GABA_B, receptor systems was examined in the learned helplessness paradigm in rats. Rats were injected with bicuculline or baclofen for 14 days. On day 14, the rats were subjected to 15 inescapable shocks. On day 15, they underwent the 40-trial escape test. Baclofen exacerbated the escape failures in the rats subjected to the inescapable shocks, although baclofen had no effects in the animals without shock pre-treatment. Bicuculline failed to influence the escape failures in the rats with the 15-shock pre-treatment. These results suggest that the long-term increase in GABA_B, neurotransmission but not the long-term attenuation of GABA_A neurotransmission may be related to helplessness in rats.     

中枢神经系统血管周细胞瘤诊治分析

目的：探讨中枢神经系统血管周细胞瘤的临床特点及其治疗方法。方法回顾分析14例中枢神经系统血管周细胞瘤患者的临床资料,随访5～100个月,并进行文献复习。结果14例患者均行手术,术后病理明确诊断。肿瘤全切除8例,大部切除3例,部分切除3例。肿瘤复发7例（50％,4例为全切除,1例大部切除,2例为部分切除,术后均未曾放疗）,中位复发时间39个月,全切术后中位复发时间41．5个月,未全切除中位复发时间17个月。复发后再次手术及术后放疗仍可获得较长时间生存。结论血管周细胞瘤诊断依赖于病理,目前手术及术后放疗是较好的治疗办法,手术切除的完整性尤为重要。     

Parallel manifestations of neuropathologies in the enteric and central nervous systems

BACKGROUND: Neurodegenerative diseases may extend outside the central nervous system (CNS) and involve the gastrointestinal (GI) tract. The gut would appear to be a pathological marker for neurodegeneration, as well as a site for studying the pathophysiology of neurodegeneration. In fact, both in the ENS and CNS, misfolded proteins are likely to initiate a process of neurodegeneration. For example, the very same protein aggregates can be detected both in the ENS and CNS. In both systems, misfolded proteins are likely to share common cell-to-cell diffusion mechanisms, which may occur through a parallel prion-like diffusion process. Independently from the enteric or central origin, misfolded proteins may proceed along the following steps, they: (i) form aggregates; (ii) are expressed on plasma membrane; (iii) are secreted extracellularly; (iv) are glycated to form advanced glycation end-products (AGEs); (v) are internalized through specific receptors placed on neighboring cells (RAGEs); (vi) are cleared by autophagy; and (vii) are neurotoxic. These features are common for a-synuclein (in Parkinson's disease and other synucleinopathies), β-amyloid and tau (in degenerative dementia), SOD-1 and TDP43 (in amyotrophic lateral sclerosis), and PrPsc (in prion diseases). While in some diseases these features are common to both ENS and CNS, in others this remains a working hypothesis. PURPOSE: This review analyzes GI alterations from a pathological perspective to assess whether the enteric nervous system (ENS) mirrors the neuropathology described in the CNS. We discuss the potential mechanisms that lead to the onset and spread of neurodegeneration within the gut, from the gut to the brain, and vice versa.