Skip to main content
SpringerLink
Log in

Selective survival of calretinin- and vasoactive-intestinal-peptide-containing nerve elements in human chagasic submucosa and mucosa

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Chronic Chagas’ disease is frequently characterized by massive myenteric neuron loss resulting in megacolon with severely and irreversibly disturbed motility. Here, we focused on two submucosal neuron populations, immunoreactive for calretinin (CALR) or somatostatin (SOM), and their respective mucosal nerve fibres in chagasic megacolon. Surgically removed megacolonic segments of seven chagasic patients were compared with seven age- and region-matched non-chagasic control segments. Evaluation included immunohistochemical triple-staining of cryosections for CALR, SOM and peripherin or for CALR and vasoactive intestinal peptide (VIP) and of submucosal whole-mounts for CALR, SOM and the pan-neuronal marker anti-HuC/D. Submucosal neuron counts in chagasic tissue revealed neuron numbers reduced to 51.2 % of control values. In cryosections, nerve fibre area measurements revealed 8.6 % nerve fibre per mucosal area in control segments, but this value decreased to 1.5 % in megacolonic segments. In both evaluations, a disproportionate decrease of SOM-reactive nerve elements was observed. The proportions of SOM-positive neurons related to the total neuron number declined to 2 % (control 10 %) and the proportion of SOM-reactive mucosal nerve fibres related to the whole mucosal area to 0.014 % (control 1.8 %)in chagasic tissue. The second set of cryosections revealed extensive colocalization of CALR with VIP in both surviving submucosal perikarya and mucosal nerve fibres. We suggest that VIP, a neuroprotective and neuroeffectory peptide typically contained in submucosal neurons, allows both the VIP-containing neurons to endure and the patients to survive by maintaining their mucosal barrier, despite the almost complete loss of colonic motility for decades.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adad SJ, Cancado CG, Etchebehere RM, Teixeira VP, Gomes UA, Chapadeiro E, Lopes ER (2001) Neuron count reevaluation in the myenteric plexus of chagasic megacolon after morphometric neuron analysis. Virchows Arch 438:254–258

    Article  PubMed  CAS  Google Scholar 

  • Beck M, Schlabrakowski A, Schrodl F, Neuhuber W, Brehmer A (2009) ChAT and NOS in human myenteric neurons: co-existence and co-absence. Cell Tissue Res 338:37–51

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A (2006) Structure of enteric neurons. Adv Anat Embryol Cell Biol 186:1–94

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Schrödl F, Neuhuber W, Hens J, Timmermans J-P (1999) Comparison of enteric neuronal morphology as demonstrated by DiI-tracing under different tissue handling conditions. Anat Embryol 199:57–62

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Schrödl F, Neuhuber W (2002) Correlated morphological and chemical phenotyping in myenteric type V neurons of porcine ileum. J Comp Neurol 453:1–9

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Blaser B, Seitz G, Schrödl F, Neuhuber W (2004a) Pattern of lipofuscin pigmentation in nitrergic and non-nitrergic, neurofilament immunoreactive myenteric neuron types of human small intestine. Histochem Cell Biol 121:13–20

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Croner R, Dimmler A, Papadopoulos T, Schrödl F, Neuhuber W (2004b) Immunohistochemical characterization of putative primary afferent (sensory) myenteric neurons in human small intestine. Auton Neurosci 112:49–59

    Article  PubMed  CAS  Google Scholar 

  • Brehmer A, Rupprecht H, Neuhuber W (2010) Two submucosal nerve plexus in human intestines. Histochem Cell Biol 133:149–161

    Article  PubMed  CAS  Google Scholar 

  • Brenneman DE (2007) Neuroprotection: a comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides 28:1720–1726

    Article  PubMed  CAS  Google Scholar 

  • Chagas C (1909) Nova Tripanozomiase humana. Mem Inst Oswaldo Cruz 1909:159-218

    Article  Google Scholar 

  • Clayton J (2010) Chagas disease 101. Nature 465:S4–S5

    Article  PubMed  Google Scholar 

  • Costa M, Brookes SJ, Steele PA, Gibbins I, Burcher E, Kandiah CJ (1996) Neurochemical classification of myenteric neurons in the guinea-pig ileum. Neuroscience 75:949–967

    Article  PubMed  CAS  Google Scholar 

  • Coura JR, Vinas PA (2010) Chagas disease: a new worldwide challenge. Nature 465:S6–S7

    Article  PubMed  Google Scholar 

  • Ekblad E, Bauer AJ (2004) Role of vasoactive intestinal peptide and inflammatory mediators in enteric neuronal plasticity. Neurogastroenterol Motil 16:123–128

    Article  PubMed  Google Scholar 

  • Furness JB (2006) The enteric nervous system. Blackwell, Oxford

    Google Scholar 

  • Furness JB, Trussel DC, Pompolo S, Bornstein JC, Smith TK (1990) Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections. Cell Tissue Res 260:261–272

    Article  PubMed  CAS  Google Scholar 

  • Furness JB, Alex G, Clark MJ, Lal VV (2003) Morphologies and projections of defined classes of neurons in the submucosa of the guinea-pig small intestine. Anat Rec A 272:475–483

    Article  Google Scholar 

  • Grider JR (1993) Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis. Am J Physiol 264:G334–G340

    PubMed  CAS  Google Scholar 

  • Hens J, Schrödl F, Brehmer A, Adriaensen D, Neuhuber W, Scheuermann DW, Schemann M, Timmermans J-P (2000) Mucosal projections of enteric neurons in the porcine small intestine. J Comp Neurol 421:429–436

    Article  PubMed  CAS  Google Scholar 

  • Iantorno G, Bassotti G, Kogan Z, Lumi CM, Cabanne AM, Fisogni S, Varrica LM, Bilder CR, Munoz JP, Liserre B, Morelli A, Villanacci V (2007) The enteric nervous system in chagasic and idiopathic megacolon. Am J Surg Pathol 31:460–468

    Article  PubMed  Google Scholar 

  • Jabari S, Silveira AB da, Oliveira EC de, Neto SG, Quint K, Neuhuber W, Brehmer A (2011) Partial, selective survival of nitrergic neurons in chagasic megacolon. Histochem Cell Biol 135:47–57

    Article  PubMed  CAS  Google Scholar 

  • Köberle F (1968) Chagas’ disease and Chagas’ syndromes: the pathology of American trypanosomiasis. Adv Parasitol 6:63–116

    Article  PubMed  Google Scholar 

  • Kramer K, Silveira AB da, Jabari S, Kressel M, Raab M, Brehmer A (2011) Quantitative evaluation of neurons in the mucosal plexus of adult human intestines. Histochem Cell Biol 136:1–9

    Article  PubMed  CAS  Google Scholar 

  • Kustermann A, Neuhuber W, Brehmer A (2011) Calretinin and somatostatin immunoreactivities label different human submucosal neuron populations. Anat Rec A 294:858–869

    Article  CAS  Google Scholar 

  • Meneghelli UG (2004) Chagasic enteropathy. Rev Soc Bras Med Trop 37:252–260

    Article  PubMed  Google Scholar 

  • Neunlist M, Toumi F, Oreschkova T, Denis M, Leborgne J, Laboisse CL, Galmiche JP, Jarry A (2003) Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways. Am J Physiol Gastrointest Liver Physiol 285:G1028–G1036

    PubMed  CAS  Google Scholar 

  • Costa RdB, De Lima Filho EC (1964) The submucous and myenteric plexuses of the human colon in Chagas’ disease. Rev Inst Med Trop Sao Paulo 6:211–218

    Google Scholar 

  • Schabadasch A (1930) Intramurale Nervengeflechte des Darmrohrs. Z Zellforsch Mikrosk Anat 10:320–385

    Article  Google Scholar 

  • Schnell SA, Staines WA, Wessendorf MW (1999) Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem 47:719–730

    Article  PubMed  CAS  Google Scholar 

  • Stach W (1981) Zur neuronalen Organisation des Plexus myentericus (Auerbach) im Schweinedünndarm. II. Typ II-Neurone. Z Mikrosk Anat Forsch 95:161–182

    PubMed  CAS  Google Scholar 

  • Toumi F, Neunlist M, Cassagnau E, Parois S, Laboisse CL, Galmiche JP, Jarry A (2003) Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture model. Neurogastroenterol Motil 15:239–242

    Article  PubMed  CAS  Google Scholar 

  • Weidmann S, Schrödl F, Neuhuber W, Brehmer A (2007) Quantitative estimation of putative primary afferent neurons in the myenteric plexus of human small intestine. Histochem Cell Biol 128:399–407

    Article  PubMed  CAS  Google Scholar 

  • Yuan A (2007) Neurofilament protein partnership, export, transport, phosphorylation and neurodegeneration. In: Arlen RK (ed) New research on neurofilament proteins. Nova Science, New York, pp 53–79

    Google Scholar 

Download references

Acknowledgements

The excellent technical assistance of Karin Löschner and Stefanie Link and of Anita Hecht, Andrea Hilpert, Hedwig Symowski and Inge Zimmermann (all Erlangen, Germany) is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Institute of Anatomy I, University of Erlangen-Nuremberg, Krankenhausstr. 9, 91054, Erlangen, Germany

    Samir Jabari, Winfried Neuhuber & Axel Brehmer

  2. Human Anatomy Sector, ICBIM, Universidade Federal de Uberlândia, Minas Gerais, Postal Code 38.400-902, Brazil

    Alexandre B. M. da Silveira

  3. Department of Surgery, Medical School, Universidade Federal de Goiás, Goiânia, Postal Code 74.605-020, Brazil

    Enio C. de Oliveira & Salustiano G. Neto

  4. Institute for Surgical Research, University of Marburg, Baldingerstr., 35043, Marburg, Germany

    Karl Quint

Authors
  1. Samir Jabari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre B. M. da Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Enio C. de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Salustiano G. Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karl Quint
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Winfried Neuhuber
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Axel Brehmer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samir Jabari.

Additional information

This work was supported by funds from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FIOCRUZ (Fundação Oswaldo Cruz), PAPES V (Programa de Apoio a Pesquisa Estratégica em Saúde) and the Deutsche Forschungsgemeinschaft (BR 1815/4-1).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jabari, S., da Silveira, A.B.M., de Oliveira, E.C. et al. Selective survival of calretinin- and vasoactive-intestinal-peptide-containing nerve elements in human chagasic submucosa and mucosa. Cell Tissue Res 349, 473–481 (2012). https://doi.org/10.1007/s00441-012-1406-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1406-8

Keywords

Search

Navigation