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Preponderance of inhibitory versus excitatory intramuscular nerve fibres in human chagasic megacolon

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Introduction

Megacolon, chronic dilation of a colonic segment, is a frequent sign of Chagas disease. It is accompanied by an extensive neuron loss which, as shown recently, results in a partial, selective survival of nitrergic myenteric neurons. Here, we focused on the balance of intramuscular excitatory (choline acetyltransferase [ChAT]-immunoreactive) and inhibitory (neuronal nitric oxide synthase [NOS]- as well as vasoactive intestinal peptide [VIP]-immunoreactive) nerve fibres.

Materials and methods

From surgically removed megacolonic segments of seven patients, three sets of cryosections (from non-dilated oral, megacolonic and non-dilated anal parts) were immunhistochemically triple-stained for ChAT, NOS and VIP. Separate area measurements of nerve profiles within the circular and longitudinal muscle layers, respectively, were compared with those of seven non-chagasic control patients. Additionally, wholemounts from the same regions were stained for NOS, VIP and neurofilaments (NF).

Results

The intramuscular nerve fibre density was significantly reduced in all three chagasic segments. The proportions of inhibitory (NOS only, VIP only, or NOS/VIP-coimmunoreactive) intramuscular nerves were 68 %/58 % (circular/longitudinal muscle, respectively) in the controls and increased to 75 %/69 % (oral parts), 84 %/76 % (megacolonic) and 87 %/94 % (anal) in chagasic specimens. In the myenteric plexus, NF-positive neurons co-staining for NOS and VIP also increased proportionally. The almost complete lack of dendritic structures in ganglia of chagasic specimens hampered morphological identification.

Discussion and conclusion

We suggest that preponderance of inhibitory, intramuscular nerve fibres may be one factor explaining the chronic dilation. Since the nerve fibre imbalance is most pronounced in the anal, non-dilated segment, other components of the motor apparatus (musculature, interstitial cells, submucosal neurons) have to be considered.

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Acknowledgments

The excellent technical assistance of Karin Löschner and Stefanie Link as well as Anita Hecht, Andrea Hilpert, Hedwig Symowski and Inge Zimmermann (all Erlangen, Germany) is gratefully acknowledged. 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 Deutsche Forschungsgemeinschaft (BR 1815/4-1).

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Alexandre B. M. da Silveira

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

    Enio C. de Oliveira

  3. Institute for Surgical Research, University of Marburg, Baldingerstrasse, 35043, Marburg, Germany

    Karl Quint

  4. Institute of Anatomy I, University of Erlangen–Nuremberg, Krankenhausstrasse 9, 91054, Erlangen, Germany

    Samir Jabari, Winfried Neuhuber & Axel Brehmer

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  1. Samir Jabari
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  2. Alexandre B. M. da Silveira
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  3. Enio C. de Oliveira
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  4. Karl Quint
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Correspondence to Samir Jabari.

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Jabari, S., da Silveira, A.B.M., de Oliveira, E.C. et al. Preponderance of inhibitory versus excitatory intramuscular nerve fibres in human chagasic megacolon. Int J Colorectal Dis 27, 1181–1189 (2012). https://doi.org/10.1007/s00384-012-1500-0

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