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 vesic les. These proproteins are actively processed into small neuroactive peptid es, which influence neurotransmitter release, microglial activation and mon ocyte 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 distributi on of chromogranin A, chromogranin B and secretoneurin, the major proteolyt ic product of secretogranin-II, have been studied by immunohistochemistry a fter 5 min of transient forebrain ischemia in the Mongolian gerbil. A stron g 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 ischem ia. 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 chromogra nin A and secretoneurin was found in selected neurons of the neocortex. Chr omogranin A and secretoneurin immunostaining patterns were similar in ische mic and control gerbils at 4 and 7 days following the ischemic insult. Chro mogranin A and secretoneurin immunoreactivity in consecutive sections showe d co-localization of both antigens but also selective overexpression of chr omogranin A or secretoneurin in various neurons. No changes in chromogranin B immunoreactivity were detected across the time course following transien t forebrain ischemia. These data indicate that changes in the expression of the chromogranin family of proteins after ischemia are selective for chrom ogranin A and secretoneurin. To our knowledge, this is the first study show ing that the expression of the chromogranin family of proteins is different ially regulated after an ischemic insult in selected neuronal populations o f the hippocampal formation and the cerebral cortex. Furthermore, the prese nt data suggest a possible implication of chromogranin A and secretoneurin in the pathophysiology of transient forebrain ischemia.