Differential regulation of chromogranin A, chromogranin B and secretoneurin protein expression after transient forebrain ischemia in the gerbil

The chromogranin/secretogranin family of proteins is widely distributed in the central nervous system, where they are stored in large dense-core vesicles. These proproteins are actively processed into small neuroactive peptides, which influence neurotransmitter release, microglial activation and monocyte migration. These properties suggest a possible role of chromogranins/secretogranins in the response that follows central nervous system injury. In the present study, the temporal pattern of expression and the distribution of chromogranin A, chromogranin B and secretoneurin, the major proteolytic product of secretogranin-II, have been studied by immunohistochemistry after 5 min of transient forebrain ischemia in the Mongolian gerbil. A strong increase in the immunoreactivity for chromogranin A and secretoneurin was found in the CA3 pyramidal cell layer of the hippocampus, starting at 12 h, with a peak at 24 h and decrease at 48 h after transient forebrain ischemia. In the hippocampal formation, a rise in chromogranin A immunoreactivity was detected in neurons of the subiculum and the granule cell layer of the dentate gyrus. In addition, increase in the immunoreactivity for chromogranin A and secretoneurin was found in selected neurons of the neocortex. Chromogranin A and secretoneurin immunostaining patterns were similar in ischemic and control gerbils at 4 and 7 days following the ischemic insult. Chromogranin A and secretoneurin immunoreactivity in consecutive sections showed co-localization of both antigens but also selective overexpression of chromogranin A or secretoneurin in various neurons. No changes in chromogranin B immunoreactivity were detected across the time course following transient forebrain ischemia. These data indicate that changes in the expression of the chromogranin family of proteins after ischemia are selective for chromogranin A and secretoneurin. To our knowledge, this is the first study showing that the expression of the chromogranin family of proteins is differentially regulated after an ischemic insult in selected neuronal populations of the hippocampal formation and the cerebral cortex. Furthermore, the present data suggest a possible implication of chromogranin A and secretoneurin in the pathophysiology of transient forebrain ischemia.