Early handling increases susceptibility to experimental autoimmune encephalomyelitis (EAE) in C57BL/6 male mice

2009 ◽  
Vol 212 (1-2) ◽  
pp. 10-16 ◽  
Author(s):  
Sandra Columba-Cabezas ◽  
Grazia Iaffaldano ◽  
Flavia Chiarotti ◽  
Enrico Alleva ◽  
Francesca Cirulli
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Male Mice ◽  
Autoimmune Encephalomyelitis ◽  
Early Handling ◽  
Experimental Autoimmune

scholarly journals Sex-Specific Effects of Microglia-Like Cell Engraftment during Experimental Autoimmune Encephalomyelitis

2020 ◽  
Vol 21 (18) ◽  
pp. 6824 ◽  
Author(s):  
Jinming Han ◽  
Keying Zhu ◽  
Kai Zhou ◽  
Ramil Hakim ◽  
Sreenivasa Raghavan Sankavaram ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Active Immunization ◽  
Inflammatory Factors ◽  
Male Mice ◽  
Autoimmune Encephalomyelitis ◽  
Cell Engraftment ◽  
Peripheral Monocyte ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in Cx3cr1CreER/+Rosa26DTA/+ mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells. In this study, tamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ and Cx3cr1CreER/+ female and male mice. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, was induced by active immunization with myelin oligodendrocyte glycoprotein (MOG) one month after tamoxifen injections in Cx3cr1CreER/+Rosa26DTA/+ mice and Cx3cr1CreER/+ mice, a time point when the CNS niche was colonized by microglia derived from both CNS microglia and peripherally-derived macrophages. We demonstrate that engraftment of microglia-like cells following microglial depletion exacerbated EAE in Cx3cr1CreER/+Rosa26DTA/+ female mice as assessed by clinical symptoms and the expression of CNS inflammatory factors, but these findings were not evident in male mice. Higher major histocompatibility complex class II expression and cytokine production in the female CNS contributed to the sex-dependent EAE severity in mice following engraftment of microglia-like cells. An underestimated yet marked sex-dependent microglial activation pattern may exist in the injured CNS during EAE.

scholarly journals Sex-Specific Effects of Microglia-Like Cell Engraftment During Experimental Autoimmune Encephalomyelitis

2020 ◽  
Author(s):  
Jinming Han ◽  
Keying Zhu ◽  
Kai Zhou ◽  
Ramil Hakim ◽  
Sreenivasa Raghavan Sankavaram ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Myeloid Cell ◽  
Active Immunization ◽  
Inflammatory Factors ◽  
Male Mice ◽  
Autoimmune Encephalomyelitis ◽  
Peripheral Monocyte ◽  
Experimental Autoimmune

Abstract BackgroundMultiple Sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in Cx3cr1CreER/+Rosa26DTA/+ mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells. MethodsTamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ and Cx3cr1CreER/+ female and male mice. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, was induced by active immunization with myelin oligodendrocyte glycoprotein one month after tamoxifen injections in Cx3cr1CreER/+Rosa26DTA/+ mice and Cx3cr1CreER/+ mice, a time point when the CNS niche was colonized by microglia derived from both CNS microglia and peripherally-derived macrophages. CNS myeloid cell compositions during acute and chronic EAE were measured by flow cytometry.ResultsWe demonstrate that engraftment of microglia-like cells following microglial depletion exacerbated EAE in Cx3cr1CreER/+Rosa26DTA/+ female mice as assessed by clinical symptoms and the expression of CNS inflammatory factors, but these findings were not evident in male mice. Higher major histocompatibility complex class II expression and cytokine production in the female CNS contributed to the sex-dependent EAE severity in mice following engraftment of microglia-like cells. ConclusionThe engraftment of microglia-like cells following microglial depletion exacerbated EAE in females. An underestimated yet marked sex-dependent microglial activation pattern may exist in the injured CNS during EAE.

scholarly journals Sex Effect on Cardiac Damage in Mice With Experimental Autoimmune Encephalomyelitis

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142199177
Author(s):  
Ruixia Wu ◽  
Yue Su ◽  
Quan Yuan ◽  
Linlin Li ◽  
Jimusi Wuri ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Inflammatory Factor ◽  
Male Mice ◽  
Cardiac Damage ◽  
Autoimmune Encephalomyelitis ◽  
Sex Effect ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Recent clinical study suggested that MS patient exhibited acute heart failure. Further, 12-lead electrocardiographic study showed a longer QTc interval in both MS patient and experimental autoimmune encephalomyelitis (EAE) Lewis rat. However, there is limited study regarding the effect of sex on cardiac injury in EAE. To our knowledge, sex effect on cardiac damage in mice with EAE has not yet been published. Herein, we examined the role of the immune system in mediating cardiac dysfunction after EAE in female and male mice. Neurological function was subsequently evaluated and cardiac function was assessed by echocardiography at multiple time points after EAE. EAE mice exhibited severe neurological deficit and significant cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 1 and 2 months after EAE induction. Meanwhile male EAE presented increased expression of the oxidative stress (e.g., nicotinamaide adenine dinucleotide phosphate oxidase-2; NOX-2) in heart, as well as cardiac hypertrophy, increased left ventricle (LV) mass and more severe cardiac fibrosis compared with male control mice. In addition, male EAE mice showed significantly increased cardiac canonical inflammatory mediator (e.g., monocyte chemoattractant protein-1; MCP-1, transforming growth factor-β; TGF-β and toll-like receptor 2; TLR-2) compared with female EAE mice at 2 months after EAE induction. In conclusion, EAE increases inflammatory factor expression and aggravates cardiac dysfunction in male mice compared with female mice, which may contribute to different cardiac outcome in EAE mice.

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