Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 4, Pages 1248-1263Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-020-0651-6
Keywords
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Funding
- Bodossakis Foundation, Athens, Greece
- Captain Fanourakis Foundation, Kos island, Greece
- General Secretariat for Research and Technology (GSRT)
- Hellenic Foundation for Research and Innovation (HFRI) [1030]
- Excellence II
- 'Research Excellence' Grant - General Secretariat for Research and Technology (GSRT) [5035]
- 'Fondation Sante' Research Grant in the Biomedical Sciences
- DINNESMIN - EU [T1EDeltaK-03186]
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This study investigates the effects of acute and chronic experimental colitis on adult hippocampal neurogenesis and innate immune cell responses. It reveals that acute colitis enhances neurogenesis but with deficits in cell cycle kinetics, while chronic colitis shows normal levels of neurogenesis but deficits in neuron migration and integration. Additionally, acute colitis leads to increased inflammation in the hippocampus, while chronic colitis results in elevated levels of tissue-repairing cells and anti-inflammatory cytokines. These findings highlight potential mechanisms underlying cognitive and mood dysfunction in patients with IBD.
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.
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