PT  - JOURNAL ARTICLE
AU  - Nicole L. Rumian
AU  - Carolyn Nicole Brown
AU  - Tara B. Hendry-Hofer
AU  - Thomas Rossetti
AU  - James E. Orfila
AU  - Jonathan E. Tullis
AU  - Linda P. Dwoskin
AU  - Olivia R. Buonarati
AU  - John E. Lisman
AU  - Nidia Quillinan
AU  - Paco S. Herson
AU  - Vikhyat S. Bebarta
AU  - K. Ulrich Bayer
TI  - Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory and is neuroprotective in non-rodents
AID  - 10.1101/2023.01.23.523316
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.23.523316
4099  - http://biorxiv.org/content/early/2023/01/23/2023.01.23.523316.short
4100  - http://biorxiv.org/content/early/2023/01/23/2023.01.23.523316.full
AB  - The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses a problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological CaMKII inhibition with tatCN19o interfered with learning in mice only mildly and transiently (for less than 1 h) and did not at all reverse pre-formed memories. This was at ≥500fold of the dose that protected hippocampal neurons from cell death after a highly clinically relevant pig model of transient global cerebral ischemia: ventricular fibrillation followed by advanced life support and electrical defibrillation to induce return of spontaneous circulation. Of additional importance for therapeutic development, cardiovascular safety studies in mice and pig did not indicate any concerns with acute tatCN19o injection. Taken together, even though prolonged interference with CaMKII signaling can erase memory, acute short-term CaMKII inhibition with tatCN19o did not cause such retrograde amnesia that would pose a contraindication for therapy.Competing Interest StatementThe authors have declared no competing interest.