The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damage
J. Clin. Invest. Wensheng Lin, et al. 117:448 doi:10.1172/JCI29571 [Go to this article.]

Figure 2
CNS delivery of IFN-γ before EAE onset protects against EAE-induced demyelination dependent on the PERK pathway. (A) MBP immunostaining showed that the CNS delivery of IFN-γ protected against EAE-induced demyelination in the lumbar spinal cords of mice on a Perk^+/+ background at PID17. In contrast, there was more severe demyelination in the lumbar spinal cord of IFN-γ^CNS+;Perk^+/– mice at PID17 compared with control mice. Scale bar: 50 μm. (B and C) Toluidine blue staining revealed that the myelin and axons in the spinal cords of IFN-γ^CNS+;Perk^+/+ mice remained almost intact at PID17. In contrast, CNS delivery of IFN-γ did not prevent demyelination and axon damage in the lumbar spinal cord of mice on a Perk^+/– background at PID17. Scale bar: 10 μm. (D and E) CC1 immunostaining showed that oligodendrocytes in the lumbar spinal cords of IFN-γ^CNS+;Perk^+/+ mice remained almost intact at PID17. In contrast, similar to control mice, IFN-γ^CNS+;Perk^+/– mice lost the majority of oligodendrocytes in the demyelinated lesions of their lumbar spinal cords at PID17. Scale bar: 25 μm. (F) Real-time PCR analysis of the mRNA level of MBP in the indicated spinal cords at PID17 relative to that in the spinal cords of age-matched naive mice. Error bars represent SD. n = 3. *P < 0.05 versus IFN-γ^CNS–;PERK^+/+ (C) or naive mice (E and F).