A diabetes mellitus (DM) pode levar a distúrbios da motilidade gastrointestinal que podem
se tornar clinicamente relevantes em alguns pacientes. Modelos de Dm em roedores
indicam anormalidades morfofuncionais do sistema nervoso entérico nessa doença. Neste
trabalho, avaliamos se o DM experimental pode levar a alterações na eferência
colinérgica excitatória, densidade neuronal e expressão dos canais de sódio voltagemdependente (Nav) no plexo mioentérico do íleo. Hiperglicemia induzida por
estreptozotocina em ratas foi desenvolvida durante oito semanas. Experimentos de
imunofluorescência de tripla marcação revelaram que a densidade de neurônios por área
do íleo no DM foi significativamente reduzida quando comparada ao controle. Foram
observadas reduções médias de 52,2% do total de neurônios (p=0,0001); 50,0% dos
neurônios colinérgicos (p=0,0068) e 54,8% dos neurônios nitrérgicos (p=0,0042). Também
foram observadas reduções significativas de neurônios por área de gânglio (28,2% do
total, p=0,0002; 27,7% de colinérgicos, p= 0,0002 e 32,1% de neurônios nitrérgicos,
p=0,0016). A densidade de fibras colinérgicas na superfície do músculo longitudinal
também foi significativamente reduzida (controle: 41 ± 2, DM: 24 ± 3%; p=0,003), embora
a análise western-blot não indicasse redução na expressão de ChAT no DM. grupo. A
isoforma Nav1.6 foi detectada em diferentes neurônios mioentéricos e a DM tendeu a
mudar o padrão de imunomarcação para neurônios de tamanho maior (297,4 ± 10 vs.
372,5 ± 8,4 µm2), mas esse efeito não foi significativo (p=0,3). Os dados de RT-qPCR não
sugeriram uma alteração dos transcritos para ChAT, nNOS, Nav1.3, Nav1.6 ou Nav1.7.
Nossos dados confirmam a visão de que o DM crônico leva à redução das fibras
colinérgicas excitatórias e da densidade neuronal. No entanto, mudanças no perfil de
expressão do canal de sódio, que poderiam levar à disfunção neuronal, não foram
detectadas. / Diabetes mellitus (DM) may lead to gastrointestinal motility disorders that may become
clinically relevant in some patients. Rodent models of DM indicate morpho-functional
abnormalities of the enteric nervous system in this disease. In this work, we have
evaluated whether experimental DM can lead to changes in excitatory cholinergic
efference, neuronal density and voltage-gate sodium channels (Nav) expression in the
myenteric plexus of ileum. Streptozotocin-induced hiperglycemia in female rats was
allowed to develop during eight weeks. Triple immunofluorescence labeling experiments
revealed that the density of neurons per area of ileum in DM was significantly reduced
when compared to the control. It were observed average reductions of 52.2% of total
neurons (p=0.0001); 50.0% of cholinergic (p=0.0068) and 54.8% of nitrergic neurons
(p=0.0042). Significant reductions of neurons per area of ganglion were also observed
(28.2% of total, p=0.0002; 27.7% of cholinergic, p=0,0002 and 32.1% of nitrergic neurons,
p=0.0016). The cholinergic fibers density at the surface of longitudinal muscle was also
significantly reduced (control: 41 ± 2, DM: 24 ± 3%; p=0.003), although western-blot
analysis did not indicate a reduction in the expression of ChAT in DM group. The Nav1.6
isoform was detected in different myenteric neurons and DM tended to shift the
immunolabeling pattern towards neurons of bigger size (297.4 ± 10 vs. 372.5 ± 8.4 m2),
but this effect was not significant (p=0.3). RT-qPCR data did not suggest an alteration of
transcripts for ChAT, nNOS, Nav1.3, Nav1.6 or Nav1.7. Our data support the view that
chronic DM leads to reduction in excitatory cholinergic fibers and neuronal density.
However, changes in sodium channel expression profiling, which could lead to neuronal
dysfunction, were not detected. / Fundação de Amparo à Pesquisa do Estado de Minas Gerais
| Identifer | oai:union.ndltd.org:IBICT/oai:localhost:tede/602 |
| Date | 20 April 2018 |
| Creators | BRASILEIRO, Amanda Damasceno |
| Contributors | RODRIGUES, Aldo Rogelis Aquiles, 83546448634, http://lattes.cnpq.br/6645292290768657 |
| Publisher | Universidade Federal do Triângulo Mineiro, Instituto de Ciências da Saúde - ICS::Curso de Medicina, Brasil, UFTM, Programa de Pós-Graduação em Ciências Fisiológicas |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | Portuguese |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFTM, instname:Universidade Federal do Triangulo Mineiro, instacron:UFTM |
| Rights | http://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess |
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