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Region-dependent effects of diabetes and insulin-replacement on neuronal nitric oxide synthase-and heme oxygenase-immunoreactive submucous neurons

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World Journal of Gastroenterology 2017年第41期23卷 7359-7368页

作者： Nikolett Bódi zita szalai Lalitha Chandrakumar Mária Bagyánszki Department of Physiology Anatomy and Neuro-science Faculty of Science and Informatics University of Szeged

AIM To investigate the intestinal segment-specific effects of diabetes and insulin replacement on the density of different subpopulations of submucous neurons. METHODS Ten weeks after the onset of type 1 diabetes samples were taken from the duodenum, ileum and colon of streptozotocin-induce diabetic, insulin-treated diabetic and sex-and age-matched control rats. Whole-mount preparations of submucous plexus were prepared from the different gut segments for quantitative fluorescent immunohistochemistry. The following double-immunostainings were performed: neuronal nitric oxide synthase(n NOS) and Hu C/D, heme oxygenase(HO) 1 and peripherin, as well as HO2 and peripherin. The density of n NOS-, HO1-and HO2-immunoreactive(IR) neurons was determined as a percentage of the total number of submucous neurons. RESULTS The total number of submucous neurons and the proportion of n NOS-, HO1-and HO2-IR subpopulations were not affected in the duodenal ganglia of control, diabetic and insulin-treated rats. While the total neuronal number did not change in either the ileum or the colon, the density of nitrergic neurons exhibited a 2-and 3-fold increase in the diabetic ileum and colon, respectively, which was further enhanced after insulin replacement. The presence of HO1-and HO2-IR submucous neurons was robust in the colon of controls(38.4%-50.8%), whereas it was significantly lower in the small intestinal segments(0.0%-4.2%, P < 0.0001). Under pathophysiological conditions the only alteration detected was an increase in the ileum and a decrease in the colon of the proportion of HO-IR neurons in insulin-treated diabetic animals. CONCLUSION Diabetes and immediate insulin replacement induce the most pronounced region-specific alterations of n NOS-, HO1-and HO2-IR submucous neuronal density in the distal parts of the gut.

关键词： Nitrergic neurons Heme oxygenase 1 Heme oxygenase 2 Submucous neurons Gut regionspecificity Diabetes Insulin

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Gut region-specific TNFR expression:TNFR2 is more affected than TNFR1 in duodenal myenteric ganglia of diabetic rats

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World Journal of Diabetes 2023年第1期14卷 48-61页

作者： Bence Pál Barta Benita Onhausz Afnan AL Doghmi zita szalai János Balázs Mária Bagyánszki Nikolett Bódi Department of Physiology Anatomy and NeuroscienceUniversity of SzegedSzeged 6726Hungary

BACKGROUND Cytokines are essential in autoimmune inflammatory processes that accompany type 1 *** necrosis factor alpha plays a key role among others in modulating enteric neuroinflammation,however,it has a dual role in cell degeneration or survival depending on different *** general,TNFR1 is believed to trigger apoptosis,while TNFR2 promotes cell *** importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy,however,the expression and alterations of different TNFRs in the gastrointestinal tract has not been *** To investigate the TNFR1 and TNFR2 expression in myenteric ganglia and their environment in different intestinal segments of diabetic *** Ten weeks after the onset of hyperglycemia,gut segments were taken from the duodenum,ileum and colon of streptozotocin-induced(60 mg/body weight kg i.p.)diabetic(n=17),insulin-treated diabetic(n=15)and sex-and age-matched control(n=15)*** plexus whole-mount preparations were prepared from different gut regions for TNFR1/HuCD or TNFR2/HuCD double-labeling fluorescent ***1 and TNFR2 expression was evaluated by post-embedding immunogold electron microscopy on ultrathin sections of myenteric *** levels were measured by enzyme-linked immunosorbent assay in muscle/myenteric plexus-containing(MUSCLE-MP)tissue homogenates from different gut segments and experimental *** A distinct region-dependent TNFRs expression was detected in *** density of TNFR1-labeling gold particles was lowest,while TNFR2 density was highest in duodenal ganglia and a decreased TNFRs expression from proximal to distal segments was observed in MUSCLE-MP *** diabetics,the TNFR2 density was only significantly altered in the duodenum with decrease in the ganglia(0.32±0.02 vs 0.45±0.04,P<0.05),while no significant changes in TNFR1 density was *** diabetic MUSCLE-MP h

关键词： Tumor necrosis factor alpha receptors Myenteric ganglia Enteric neurons Neuronal environment Diabetes Insulin

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World Journal of Diabetes 2021年第5期12卷 658-672页

作者： Nikolett Bódi Diána Mezei Payal Chakraborty zita szalai Bence Pál Barta János Balázs Zsolt Rázga Edit Hermesz Mária Bagyánszki Department of Physiology Anatomy and NeuroscienceFaculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of Biochemistry and Molecular Biology Faculty of Science and InformaticsUniversity of SzegedSzeged 6726Hungary Department of Pathology Faculty of MedicineUniversity of SzegedSzeged 6720Hungary

BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9(MMP9) and its tissue inhibitor(TIMP1) are essential in regulating extracellular matrix *** To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 *** Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex-and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Wholemount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid(m RNA) level was measured by quantitative polymerase chain *** Ten weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tenden

关键词： Type 1 diabetes Diabetic enteric neuropathy Neuronal microenvironment Basement membrane Matrix metalloproteinase 9 Tissue inhibitor of metalloproteinase 1

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