Chromogranin A-like immunoreactivity in the human brain: distribution in bulbar medulla and cerebral cortex

Chromogranin A is a glycoprotein stored in secretory granules of a variety of neuroendocrine cells. Among other functions, chromogranin A is a calcium-binding protein, and a precursor of modulatory peptides. Although known to be expressed in mammalian CNS neurons, it was previously believed that antibodies directed against human chromogranin A did not label neurons. A method is reported for the immunohistochemical demonstration of chromogranin A-like immunoreactivity in adult human post-mortem brain, utilizing the previously characterized monoclonal antibody LK2H10. Chromogranin A-like immunoreactivity of human brain could be absorbed with heat-stable protein extract from adrenal medulla, but not from liver, and a similar preparation of human cerebral cortex eliminated the labeling of adrenal medulla by LK2H10. However, unlike adrenal medullary chromogranin A-like immunoreactivity, cerebral chromogranin A-like immunoreactivity was destroyed by embedding the tissue in paraffin or treating frozen sections with methanol during the endogenous peroxidase blocking step, suggesting differences in post-translational processing of these two forms of chromogranin A. In both cerebral regions studied, bulbar medulla and parietal cortex, chromogranin A-like immunoreactivity was widespread in neuronal perikarya, dendrites, and axonic terminals, but restricted to certain neuronal populations. Among other findings it is reported that the main olivary neurons are immunoreactive for chromogranin A; this implies a new co-localization of chromogranin A, with corticotropin-releasing factor. The cerebral neocortex showed a laminar pattern of staining of perikarya in layers III-VI, and of the neuropil in the supragranular layers. In conjunction with the evidence of neuromodulatory action in the periphery, these results raise the possibility of a major neurotransmitter role for chromogranin A in the human brain.