Recovery of protein synthesis in tolerance-induced hippocampal CA1 neurons after transient forebrain ischemia

Abstract

Protein synthesis at various recirculation times after 5-min transient forebrain ischemia was evaluated in gerbil hippocampal CA1 pyramidal neurons that had acquired tolerance to delayed-type ischemic injury. Evaluation was performed by observing polyribosomes under electron microscopy, and by [14C]leucine autoradiography. Hippocampal CA1 pyramidal neurons in the gerbils acquired stable and reproducible tolerance to delayed-type ischemic injury subsequent to a 5-min ischemia by pretreatment that consisted of loading two 2-min ischemic periods at a 1-day interval, followed by 48 h of recirculation. During the early phase following the 5-min ischemia, polyribosomal disaggregation, loss of dendritic microtubules, and significant suppression of radiolabeled leucine incorporation were observed in the tolerance-induced CA1 neurons as well as in the non-tolerance-induced neurons. While these findings persisted in the non-tolerance-induced neurons throughout the duration of the experiment, most of the tolerance-induced neurons demonstrated reaggregation of cytosomal ribosomes, increase in the number of dendritic microtubules, and restoration of impaired amino acid incorporation 24 h after the ischemia. These findings suggest that recovery of protein synthesis during the early post ischemic phase is essential for CA1 neuron survival after ischemic injury.