Hippocampal neural stem cells and microglia response to experimental inflammatory bowel disease (IBD).

Autor: Gampierakis IA; Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.; Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Greece., Koutmani Y; Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Semitekolou M; Cellular Immunology Laboratory, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Morianos I; Cellular Immunology Laboratory, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Polissidis A; Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Katsouda A; Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.; School of Pharmacy, University of Athens, Athens, Greece., Charalampopoulos I; Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Greece.; Institute of Molecular Biology & Biotechnology (IMBB), Foundation of Research & Technology Hellas (FORTH), Heraklion, Greece., Xanthou G; Cellular Immunology Laboratory, Center for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece., Gravanis A; Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Greece.; Institute of Molecular Biology & Biotechnology (IMBB), Foundation of Research & Technology Hellas (FORTH), Heraklion, Greece., Karalis KP; Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. katia.karalis@emulatebio.com.; Emulate, Inc., 27 Drydock Avenue, Boston, MA, 02210, USA. katia.karalis@emulatebio.com.; Endocrine Division, Children's Hospital, Harvard Medical School, Boston, MA, USA. katia.karalis@emulatebio.com.; Institute for Fundamental Biomedical Research, Biomedical Science Research Centre 'Alexander Fleming', Athens, Greece. katia.karalis@emulatebio.com.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2021 Apr; Vol. 26 (4), pp. 1248-1263. Date of Electronic Publication: 2020 Jan 22.
DOI: 10.1038/s41380-020-0651-6
Abstrakt: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a disease associated with dysbiosis, resulting in compromised intestinal epithelial barrier and chronic mucosal inflammation. Patients with IBD present with increased incidence of psychiatric disorders and cognitive impairment. Hippocampus is a brain region where adult neurogenesis occurs with functional implications in mood control and cognition. Using a well-established model of experimental colitis based on the administration of dextran sodium sulfate (DSS) in the drinking water, we sought to characterize the short and long-term effects of colitis on neurogenesis and glia responses in the hippocampus. We show that acute DSS colitis enhanced neurogenesis but with deficits in cell cycle kinetics of proliferating progenitors in the hippocampus. Chronic DSS colitis was characterized by normal levels of neurogenesis but with deficits in the migration and integration of newborn neurons in the functional circuitry of the DG. Notably, we found that acute DSS colitis-induced enhanced infiltration of the hippocampus with macrophages and inflammatory myeloid cells from the periphery, along with elevated frequencies of inflammatory M1-like microglia and increased release of pro-inflammatory cytokines. In contrast, increased percentages of tissue-repairing M2-like microglia, along with elevated levels of the anti-inflammatory cytokine, IL-10 were observed in the hippocampus during chronic DSS colitis. These findings uncover key effects of acute and chronic experimental colitis on adult hippocampal neurogenesis and innate immune cell responses, highlighting the potential mechanisms underlying cognitive and mood dysfunction in patients with IBD.
Databáze: MEDLINE
Externí odkaz: