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.