TY - JOUR
T1 - Thyroid hormone and thyromimetics inhibit myelin and axonal degeneration and oligodendrocyte loss in EAE
AU - Chaudhary, Priya
AU - Marracci, Gail
AU - Calkins, E.
AU - Pocius, E.
AU - Bensen, A. L.
AU - Scanlan, T. S.
AU - Emery, B.
AU - Bourdette, D. N.
N1 - Funding Information:
This research was supported by the National Multiple Sclerosis Society grants RG 5199A4 and RG-1607-25053 to DB, RG 5106A1/1 to BE), the Race to Erase MS to DB, the OHSU Laura Fund for Innovation in Multiple Sclerosis to DB and TSS and NIH DK52798 to TSS. We would like to thank Advanced Light Microscopy Core and Electron Microscopy Core supported by the NIH, P30 NS061800. We would also like to thank the VA Portland Health Care System for providing animal husbandry, equipment support and laboratory space.
Funding Information:
This research was supported by the National Multiple Sclerosis Society grants RG 5199A4 and RG-1607-25053 to DB, RG 5106A1/1 to BE), the Race to Erase MS to DB, the OHSU Laura Fund for Innovation in Multiple Sclerosis to DB and TSS and NIH DK52798 to TSS. We would like to thank Advanced Light Microscopy Core and Electron Microscopy Core supported by the NIH , P30 NS061800 . We would also like to thank the VA Portland Health Care System for providing animal husbandry, equipment support and laboratory space.
Publisher Copyright:
© 2020 The Authors
PY - 2021/3/15
Y1 - 2021/3/15
N2 - We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4 mg/kg), Sob (5 mg/kg) or Sob-AM2 (5 mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.
AB - We have previously demonstrated that thyromimetics stimulate oligodendrocyte precursor cell differentiation and promote remyelination in murine demyelination models. We investigated whether a thyroid receptor-beta selective thyromimetic, sobetirome (Sob), and its CNS-targeted prodrug, Sob-AM2, could prevent myelin and axonal degeneration in experimental autoimmune encephalomyelitis (EAE). Compared to controls, EAE mice receiving triiodothyronine (T3, 0.4 mg/kg), Sob (5 mg/kg) or Sob-AM2 (5 mg/kg) had reduced clinical disease and, within the spinal cord, less tissue damage, more normally myelinated axons, fewer degenerating axons and more oligodendrocytes. T3 and Sob also protected cultured oligodendrocytes against cell death. Thyromimetics thus might protect against oligodendrocyte death, demyelination and axonal degeneration as well as stimulate remyelination in multiple sclerosis.
KW - EAE
KW - Inflammation
KW - Myelin
KW - Oligodendrocytes
KW - Thyromimetics
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U2 - 10.1016/j.jneuroim.2020.577468
DO - 10.1016/j.jneuroim.2020.577468
M3 - Article
C2 - 33422763
AN - SCOPUS:85098999255
VL - 352
JO - Advances in Neuroimmunology
JF - Advances in Neuroimmunology
SN - 0165-5728
M1 - 577468
ER -