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. 2024 Sep 28;13(19):1626.
doi: 10.3390/cells13191626.

Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus

Gabriela Mandú Gimenes  1 , Joice Naiara Bertaglia Pereira  2 , Eliane Borges da Silva  1 , Alef Aragão Carneiro Dos Santos  1 , Thais Martins Rodrigues  1 , Giovanna de Oliveira Santana  1 , Maria Vitoria Martins Scervino  1 , Tania Cristina Pithon-Curi  1 , Sandro Massao Hirabara  1 , Renata Gorjão  1 , Rui Curi  1   2
Affiliations

Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus

Gabriela Mandú Gimenes et al. Cells. .

Abstract

Diabetes mellitus is associated with changes in intestinal morphology and the enteric nervous system. We previously reported constipation in Goto-Kakizaki (GK) rats, a non-obese model for type 2 diabetes mellitus.

Aim: The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated.

Methods: The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured.

Results: The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum.

Conclusion: The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.

Keywords: Goto-Kakizaki rats; cholinergic neuron; constipation; enteric nervous system; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the animal groups (Wistar and GK), experimental protocol, and analyses. Eleven male rats were randomly allocated into six control (Wistar) and five experimental (GK) groups. At seventeen weeks of age, all 11 control and experimental animals were weighed, euthanized by CO2 inhalation, and decapitated. Following euthanasia, the duodenum, jejunum, distal ileum, and proximal and distal colon were collected and processed for morphometrics analysis of the myenteric plexus.
Figure 2
Figure 2
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + ChAT (red) of the Wistar and Goto-Kakizaki (GK) rats of 120 days of the duodenum, jejunum, and ileum. Arrows indicate HuC/D+ neurons, and asterisks indicate HuC/D + ChAT neurons. Objective: 20×. Bar: 50 μm.
Figure 3
Figure 3
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + ChAT (red) of the Wistar and GK rats of 120 days of the proximal and distal colon. Arrows indicate HuC/D+ neurons, and asterisks indicate HuC/D + ChAT neurons. Objective: 20×. Bar: 50 μm.
Figure 4
Figure 4
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + nNOS (red) of the Wistar and Goto-Kakizaki (GK) rats of 120 days of the duodenum, jejunum, and ileum. Arrows indicate HuC/D+ neurons, and asterisks indicate HuC/D + nNOS neurons. Objective: 20×. Bar: 50 μm.
Figure 5
Figure 5
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + nNOS (red) of the Wistar and Goto-Kakizaki (GK) animals of 120 days of the proximal and distal colon. Arrows indicate HuC/D+ neurons, and asterisks indicate HuC/D + nNOS neurons. Objective: 20×. Bar: 50 μm.
Figure 6
Figure 6
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + S100 (red) of the Wistar and Goto-Kakizaki (GK) rats of 120 days of the duodenum, jejunum, and ileum. Arrows indicate HuC/D+ neurons, and asterisks indicate enteric glial cells. Objective: 20×. Bar: 50 μm.
Figure 7
Figure 7
Representative photomicrograph of the results obtained by the immunofluorescence technique for the double staining HuC/D (green) + S100 (red) of the Wistar and Goto-Kakizaki (GK) rats of 120 days of the proximal and distal colon. Arrows indicate HuC/D+ neurons, and asterisks indicate enteric glial cells. Objective: 20×. Bar: 50 μm.
Figure 8
Figure 8
Frequency histogram (%) of the cell body area (µm2) of the myenteric neurons of the small intestine of 120-day-old animals of the HuC/D (A–C), ChAT (D–F) and nNOS populations (G–I). The number of animals used was 4 to 5.
Figure 9
Figure 9
Frequency histogram (%) of the cell body area (µm2) of the myenteric neurons of the large intestine of 120-day-old animals of the HuC/D (A,B), ChAT (C,D) and nNOS populations (E,F). The number of animals used was 4 to 5.
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