Repetitive spreading depolarization induces gene expression changes related to synaptic plasticity and neuroprotective pathways

• DOI: 10.3389/fncel.2023.1292661
• Publication Date: 2023-12-14T15:30:03Z
• Authors: Michela Dell’Orco; Jordan E. Weisend; Nora I. Perrone-B...; Andrew P. Carlson; Russell A. Morton; David N. Linsenbardt; C. William Shuttl...
• Keywords: Immediate early gene

Spreading depolarization (SD) is a slowly propagating wave of profound that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences SD, there uncertainty surrounding potential activation beneficial pathways such as cell survival and plasticity. The present study used unbiased assessments gene expression to evaluate compensatory repair mechanisms could be recruited following regardless induction method, which prior this work had not assessed. We also tested assumptions appropriate controls spatial extent changes are important for in vivo SD models. clusters were induced with either KCl focal application or optogenetic stimulation healthy mice. Cortical RNA was extracted sequenced identify differentially expressed genes (DEGs). SDs using both methods significantly upregulated 16 (vs. sham animals) included proliferation-related FOS, JUN, DUSP6, plasticity-related ARC HOMER1, inflammation-related PTGS2, EGR2, NR4A1. contralateral hemisphere commonly control tissue DEG studies, but its activity modified by near-global disruption adjacent brain. found 21 when comparing SD-involved cortex vs. from same animals. Interestingly, almost complete overlap (21/16) DEGs identified controls. Neuronal differs initiation zones, where sustained global required initiate events. varied function distance site, greater differences observed regions further away. Functional pathway enrichment analyses axonogenesis, branching, neuritogenesis, dendritic growth enriched overlapping DEGs. Increased SD-induced associated predicted inhibition death, apoptosis. These results novel biological involved plasticity and/or circuit modification brain impacted SD. functional targets determine roles recovery peri-infarct tissues.