Loss of astrocyte connexins 43 and 30 does not significantly alter susceptibility or severity of acute experimental autoimmune encephalomyelitis in mice

Abstract

We showed previously that mice deficient in astrocyte gap junctions Cx43 and Cx30 exhibit white matter vacuolation and hypomyelination. In this study we tested the hypothesis that loss of astrocytic gap junction proteins leads to exacerbation of the primary demyelinating diseases, using experimental autoimmune encephalomyelitis (EAE) as a model system. To test for this, Cx43 floxed mice were crossed with GFAP:Cre, Cx30 null mice to generate mice lacking astrocytic expression of both Cx43 and Cx30 (dKO). EAE was induced using myelin oligodendrocyte glycoprotein (MOG35-55) peptide, and mice were monitored for acute expression of disease. No statistically significant difference in clinical or pathological expression of EAE was observed. Lesion load and susceptibility of different areas of the CNS to inflammation were similar in all genotypes. Moreover, no differences were noted in blood-brain barrier (BBB) permeability, tissue wet weight, axonal pathology, gliosis or demyelination during acute disease. These data show that loss of the astrocytic connexins, Cx43 and Cx30, and the white matter pathology observed in these mice does not statistically affect clinical or pathological expression of EAE and show that astrocyte gap junctions do not regulate autoimmune inflammation and associated BBB disruption in acute EAE.

Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

“…We induced active MOG 35–55 EAE (Lutz et al, 2012) in Tg eGFP-Claudin5 +/− mice, and assessed TJ structure by two-photon microscopy at three stages of disease: 1) prior to clinical signs (EAE score 0, 6–7 days post-immunization [dpi]), 2) in mice with tail paralysis (score 1, 10 dpi), and 3) in mice with hind limb weakness/paralysis (score 2–3, 13–15 dpi). All animals with EAE have significantly more protrusions than healthy controls (i.e.…”

“…Control animals received B. pertussis toxin and emulsion containing PBS/CFA without MOG. Mice were examined for clinical EAE signs using the following scale, with 0.5-point gradations for intermediate presentation: 0, no signs; 1, flaccid tail; 2, hind limb paresis; 3, hind limb paralysis; 4, hind limb and forelimb paralysis; 5, moribund (Lutz et al, 2012). …”

Endothelial Wnt/β-catenin signaling reduces immune cell infiltration in multiple sclerosis

“…EAE was induced in female mice with MOG . Clinical signs of EAE were scored as follows: 0, no signs; 1, completely flaccid tail; 2, hind limb paresis; 3, hind limb paralysis; 4, hind limb and forelimb paralysis; 5, moribund (85,86). Patient tissue specimens (SI Appendix, Table S2) Paraffin-embedded brain tissues were used to assess SOX17 expression.…”

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion

“…EAE was induced in mice as previously described (26). Briefly, 10-to 12-wk-old male mice were immunized subcutaneously in the lower dorsum with 300 μg myelin oligodendrocyte glycoprotein (MOG ) peptide (MEVGWYRSPFSRVVHLYRNGK; Celtek Bioscience, Nashville, TN, USA) in a 200 μL emulsion of incomplete Freund adjuvant (IFA) containing 5 mg/mL Myco bacterium tuberculosis H37RA (Difco Laboratories, Detroit, MI, USA).…”