Attenuating the endoplasmic reticulum stress response improves functional recovery after spinal cord injury

• DOI: 10.1002/glia.21191
• Publication Date: 2011-06-03T12:14:23Z
• Authors: Sujata Saraswat Ohri; Melissa A. Maddie; Yongmei Zhao; Mengsheng S. Qiu; Michal Hetman; Scott R. Whittemore
• Keywords: Mice, Knockout; 0301 basic medicine; Analysis of Variance; Caspase 3; Eukaryotic Initiation Factor-2; Apoptosis; Myelin Basic Protein; Nerve Tissue Proteins; Oligodendrocyte Transcription Factor 2; Endoplasmic Reticulum Stress; Activating Transcription Factor 4; Nerve Fibers, Myelinated; DNA-Binding Proteins; Mice, Inbred C57BL; Disease Models, Animal; Mice; Oligodendroglia; 03 medical and health sciences; Basic Helix-Loop-Helix Transcription Factors; Animals; Female; Locomotion

Activation of the unfolded protein response (UPR) is involved in pathogenesis numerous CNS myelin abnormalities; yet, its direct role traumatic spinal cord injury (SCI)-induced demyelination not known. The UPR an evolutionarily conserved cell defense mechanism initiated to restore endoplasmic reticulum homeostasis various cellular stresses including infection, trauma, and oxidative damage. However, if uncompensated, triggers apoptotic death. We demonstrate that three signaling branches PERK, ATF6, IRE1α are rapidly a mouse model contusive SCI specifically at epicenter. Immunohistochemical analyses markers revealed neurons, appeared 6 24-h post-SCI. In contrast, oligodendrocytes astroglia, persisted least for up 3 days UPR-associated proapoptotic transcriptional regulator CHOP was among upregulated neurons oligodendrocytes, but astrocytes, traumatized cords. To directly analyze SCI, WT null mice received moderate T9 injury. Deletion led overall attenuation after SCI. Furthermore, hindlimb locomotion demonstrated significant functional recovery correlated with increase white-matter sparing, transcript levels basic protein, Claudin 11 decreased oligodendrocyte apoptosis contrast animals. Thus, our study provides evidence contributes loss © 2011 Wiley-Liss, Inc.