Oxygen/glucose-deprivation causes long-term impairment of synaptic CaMKII movement

Abstract

Learning and memory are thought to require hippocampal long-term potentiation (LTP), a form of synaptic plasticity that is persistently impaired after cerebral ischemia and that requires movement of the Ca2+/calmodulin-dependent protein kinase II (CaMKII) to excitatory synapses. We show here that oxygen/glucose-deprivation (OGD) in cultures hippocampal neurons causes a long-lasting impairment of CaMKII movement. Notably, CaMKII inhibition at 30 min after onset of OGD prevented the impairment in CaMKII movement. Thus, CaMKII mediates both, LTP mechanisms and their ischemia-induced impairment. These findings provide a mechanism by which ischemic conditions can impair LTP and explain how CaMKII inhibition after cerebral ischemia can prevent these LTP impairments.

Competing Interest Statement

K.U.B. is co-founder and board member of Neurexis Therapeutics, a company that seeks to develop a CaMKII inhibitor into a therapeutic drug for cerebral ischemia. O.R.B. is COO of the same company (using a different name, Olivia Asfaha, in that role). K.U.B. and N.Q. are named inventors on related patent applications by the Regents of the University of Colorado.