RT Journal Article
SR Electronic
T1 Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory and is neuroprotective in non-rodents
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.23.523316
DO 10.1101/2023.01.23.523316
A1 Nicole L. Rumian
A1 Carolyn Nicole Brown
A1 Tara B. Hendry-Hofer
A1 Thomas Rossetti
A1 James E. Orfila
A1 Jonathan E. Tullis
A1 Linda P. Dwoskin
A1 Olivia R. Buonarati
A1 John E. Lisman
A1 Nidia Quillinan
A1 Paco S. Herson
A1 Vikhyat S. Bebarta
A1 K. Ulrich Bayer
YR 2023
UL http://biorxiv.org/content/early/2023/01/23/2023.01.23.523316.abstract
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.