TY - JOUR T1 - Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory and is neuroprotective in non-rodents JF - bioRxiv DO - 10.1101/2023.01.23.523316 SP - 2023.01.23.523316 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 Y1 - 2023/01/01 UR - http://biorxiv.org/content/early/2023/01/23/2023.01.23.523316.abstract N2 - 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. ER -