Protein kinase C epsilon delays latency until anoxic depolarization through arc expression and GluR2 internalization.

Global cerebral ischemia is a debilitating injury that damages the CA1 region of the hippocampus, an area important for learning and memory. Protein kinase C epsilon activation is a critical component of many neuroprotective treatments. The ability of activation to regulate AMPA receptors (AMPARs) remains unexplored despite the role of AMPARs in excitotoxicity after brain ischemia. We determined that duanyu1531ɛ activation increased expression of a protein linked to learning and memory, activity-regulated cytoskeleton-associated protein (arc). Also, arc is necessary for neuroprotection and confers protection through decreasing AMPAR currents via GluR2 internalization. In vivo, activation of duanyu1531ɛ increased arc expression through a BDNF/TrkB pathway, and decreased GluR2 mRNA levels. In hippocampal cultured slices, duanyu1531ɛ activation decreased AMPAR current amplitudes in an arc- and GluR2-dependent manner. Additionally, duanyu1531ɛ activation triggered an arc- and GluR2 internalization-dependent delay in latency until anoxic depolarization. Inhibiting arc also blocked neuroprotection against lethal oxygen and glucose deprivation. These data characterize a novel mechanism that for the first time defines a role for arc and AMPAR internalization in conferring neuroprotection.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}