4.5 Article

Remote and Persistent Alterations in Glutamate Receptor Subunit Composition Induced by Spreading Depolarizations in Rat Brain

Journal

CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 42, Issue 4, Pages 1253-1260

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-020-01000-3

Keywords

Spreading depolarization; Spreading depression; Glutamate receptor; Plasticity; Brain injury

Funding

  1. NIH/NINDS [K08NS110988]

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This study reveals that spreading depolarizations (SDs) in healthy brain tissue can lead to changes in glutamate receptor subunit expression, potentially playing a role in brain plasticity.
Spreading depolarizations (SDs) are massive breakdowns of ion homeostasis in the brain's gray matter and are a necessary pathologic mechanism for lesion development in various injury models. However, injury-induced SDs also propagate into remote, healthy tissue where they do not cause cell death, yet their functional long-term effects are unknown. Here we induced SDs in uninjured cortex and hippocampus of Sprague-Dawley rats to study their impact on glutamate receptor subunit expression after three days. We find that both cortical and hippocampal tissue exhibit changes in glutamate receptor subunit expression, including GluA1 and GluN2B, suggesting that SDs in healthy brain tissue may have a role in plasticity. This study is the first to show prolonged effects of SDs on glutamate signaling and has implications for neuroprotection strategies aimed at SD suppression.

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