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


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.


CONCLUSIONS
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.
Institute of Anatomy I, University of Erlangen-Nuremberg, Erlangen, Germany. samir.jabari@anatomie1.med.uni-erlangen.de
Samir
S
Jabari
Alexandre B M
AB
da Silveira
Enio C
EC
de Oliveira
Karl
K
Quint
Winfried
W
Neuhuber
Axel
A
Brehmer
D000368:Aged; D014355:Chagas Disease / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008531:Megacolon / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D008875:Middle Aged; D009132:Muscles / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D009197:Myenteric Plexus / Q000473:pathology; D009412:Nerve Fibers / Q000201:enzymology / Q000473:pathology*; D009433:Neural Inhibition; D009474:Neurons / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D014660:Vasoactive Intestinal Peptide; D052248:Nitric Oxide Synthase Type I; D002795:Choline O-Acetyltransferase