Absence of Microglial Activation and Maintained Hippocampal Neurogenesis in a Transgenic Mouse Model of Crohn’s Disease

Masanetz RK, Mundlos H, Stolzer I, Winkler J, Günther C, Süß P (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cells MDPI

Book Volume: 14

Article Number: 841

Journal Issue: 11

DOI: 10.3390/cells14110841

Abstract

Adult neurogenesis in the hippocampal dentate gyrus (DG) is not only essential for learning and pattern separation, but it is also involved in emotional regulation. This process is vulnerable to local and peripheral inflammation, which is partly mediated by microglia in the DG. As Crohn’s disease (CD) is associated with neuropsychiatric comorbidity, including depression and cognitive impairment, a reduction in adult hippocampal neurogenesis by chronic gut-derived inflammation has been hypothesized. Here, we present the first study that examined the influence of chronic ileocolitis on microglia in the DG and on adult hippocampal neurogenesis in a transgenic mouse model of CD, which is generated by a constitutive knockout of caspase 8 in intestinal epithelial cells (IECs, Casp8^ΔIEC mice). Structural and transcriptional analyses revealed that microglial cell proliferation and density in the DG as well as the expression of genes associated with their homeostasis and activation in the forebrain were maintained in 14- and 24-week-old Casp8^ΔIEC mice compared to Casp8^fl controls. Furthermore, different stages of adult hippocampal neurogenesis, including progenitor cell proliferation, maturation, and apoptosis of newly generated cells, were predominantly unaffected by chronic ileocolitis, except a potential minor phenotypic shift in maturating cells in 24-week-old mice. Together, we demonstrate largely preserved adult hippocampal neurogenesis, lacking signs of local inflammatory microglial activation despite chronic inflammation of the gut.

Authors with CRIS profile

Rebecca Katharina Masanetz Department of Molecular Neurology Hanna Mundlos Department of Molecular Neurology Iris Stolzer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Jürgen Winkler Professur für Molekulare Neurologie Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Patrick Süß Department of Molecular Neurology

How to cite

APA:

Masanetz, R.K., Mundlos, H., Stolzer, I., Winkler, J., Günther, C., & Süß, P. (2025). Absence of Microglial Activation and Maintained Hippocampal Neurogenesis in a Transgenic Mouse Model of Crohn’s Disease. Cells, 14(11). https://doi.org/10.3390/cells14110841

MLA:

Masanetz, Rebecca Katharina, et al. "Absence of Microglial Activation and Maintained Hippocampal Neurogenesis in a Transgenic Mouse Model of Crohn’s Disease." Cells 14.11 (2025).

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