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Gut–Brain Axis: Insights from Hippocampal Neurogenesis and Brain Tumor Development in a Mouse Model of Experimental Colitis Induced by Dextran Sodium Sulfate

TitleGut–Brain Axis: Insights from Hippocampal Neurogenesis and Brain Tumor Development in a Mouse Model of Experimental Colitis Induced by Dextran Sodium Sulfate
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2022
AuthorsVitali, Roberta, Prioreschi C., L. Rebenaque Lorenzo, Colantoni Eleonora, Giovannini Daniela, Frusciante Sarah, Diretto Gianfranco, Marco-Jiménez F., Mancuso Mariateresa, Casciati Arianna, and Pazzaglia Simonetta
JournalInternational Journal of Molecular Sciences
Keywordsadult, Amino Acid, animal cell, animal experiment, animal model, animal tissue, article, blood brain barrier, body weight loss, brain cancer, brain dysfunction, brain-gut axis, carcinogenesis, cell proliferation, colon tissue, comparative study, controlled study, dentate gyrus, Dextran Sulfate, dextran sulfate sodium-induced colitis, hippocampal tissue, hippocampus, immunohistochemistry, in vivo study, inducible nitric oxide synthase, interleukin 1beta, interleukin 6, intestine mucosa, Ki 67 antigen, lipid, macrophage, male, medulloblastoma, metabolome, metabolomics, mouse, nervous system development, nervous system inflammation, nonhuman, Oxidative stress, pilot study, protein expression, protein S 100, Smad3 protein, thiamine, transforming growth factor beta

Chronic inflammatory bowel disorders (IBD) are idiopathic diseases associated with altered intestinal permeability, which in turn causes an exaggerated immune response to enteric antigens in a genetically susceptible host. A rise in psych cognitive disorders, such as anxiety and depression, has been observed in IBD patients. We here report investigations on a model of chemically induced experimental colitis by oral administration of sodium dextran sulfate (DSS) in C57BL/6 mice. We investigate, in vivo, the crosstalk between the intestine and the brain, evaluating the consequences of intestinal inflammation on neuroinflammation and hippocampal adult neurogenesis. By using different DSS administration strategies, we are able to induce acute or chronic colitis, simulating clinical characteristics observed in IBD patients. Body weight loss, colon shortening, alterations of the intestinal mucosa and fecal metabolic changes in amino acids-, lipid- and thiamine-related pathways are observed in colitis. The activation of inflammatory processes in the colon is confirmed by macrophage infiltration and increased expression of the proinflammatory cytokine and oxidative stress marker (Il-6 and iNOS). Interestingly, in the hippocampus of acutely DSS-treated mice, we report the upregulation of inflammatory-related genes (Il-6, Il-1β, S-100, Tgf-β and Smad-3), together with microgliosis. Chronic DSS treatment also resulted in neuroinflammation in the hippocampus, indicated by astrocyte activation. Evaluation of stage-specific neurogenesis markers reveals deficits in the dentate gyrus after acute and chronic DSS treatments, indicative of defective adult hippocampal neurogenesis. Finally, based on a possible causal relationship between gut-related inflammation and brain cancer, we investigate the impact of DSS-induced colitis on oncogenesis, using the Ptch1+/−/C57BL/6 mice, a well-established medulloblastoma (MB) mouse model, finding no differences in MB development between untreated and DSS-treated mice. In conclusion, in our experimental model, the intestinal inflammation associated with acute and chronic colitis markedly influences brain homeostasis, impairing hippocampal neurogenesis but not MB oncogenesis. © 2022 by the authors.


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Citation KeyVitali2022