title: Long-term effects of autoimmune CNS inflammation on adult hippocampal neurogenesis.
abstract: Neurogenesis is a well-characterized phenomenon within the dentate gyrus (DG) of the adult hippocampus. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of chronic inflammation remains controversial. In this study the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis was used to investigate the long-term effects of T cell-mediated central nervous system inflammation on hippocampal neurogenesis. 5-Bromodeoxyuridine (BrdU)-labeled subpopulations of hippocampal cells in EAE and control mice (coexpressing GFAP, doublecortin, NeuN, calretinin, and S100) were quantified at the recovery phase, 21 days after BrdU administration, to estimate alterations on the rate and differentiation pattern of the neurogenesis process. The core features of EAE mice DG are (i) elevated number of newborn (BrdU+) cells indicating vigorous proliferation, which in the long term subsided; (ii) enhanced migration of newborn cells into the granule cell layer; (iii) increased level of immature neuronal markers (including calretinin and doublecortin); (iv) trending decrease in the percentage of newborn mature neurons; and (v) augmented gliogenesis and differentiation of newborn neural precursor cells (NPCs) to mature astrocytes (BrdU+/S100+). Although the inflammatory environment in the brain of EAE mice enhances the proliferation of hippocampal NPCs, in the long term neurogenesis is progressively depleted, giving prominence to gliogenesis. The discrepancy between the high number of immature cells and the low number of mature newborn cells could be the result of a caused defect in the maturation pathway. © 2016 Wiley Periodicals, Inc.
authors: Laboratory of Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors: Aggeliki
authors: A
authors: Giannakopoulou
authors: Department of Historical Geology and Palaeontology, Faculty of Geology and Geoenvironment, University of Athens, Athens, Greece.
authors: George A
authors: GA
authors: Lyras
authors: Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece.
authors: Nikolaos
authors: N
authors: Grigoriadis
mesh_terms: D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D013997:Time Factors
keywords: AB_10013382; AB_10013383; AB_10013660; AB_10807945; AB_2068506; AB_2142366; AB_2230227; AB_2336382; AB_2336820; AB_2534088; AB_2534117; AB_2535849; RRIDs:IMSR_JAX:000664; SCR_002865; SCR_007369; experimental autoimmune encephalomyelitis; multiple sclerosis; neural stem cells; neuronal differentiation; neuronal proliferation