Immunohistochemistry of neuron-specific and glia-specific proteins

This paper reviews the immunohistochemical distribution of four brain-derived proteins, NSE, NFP, spot 35 and S-100 protein, in neuronal and paraneuronal tissues, concentrating on the results of our own research group. Neuron-specific enolase (NSE), a brain-specific isozyme of the glycolytic enzyme enolase, is characterized by its consistent occurrence in the cytoplasm of mature neurons. Immunoreactivity for NSE has been found in almost all paraneurons of both sensory and endocrine nature, suggesting that a unique system of intracellular energy metabolism may be shared by neurons and paraneurons. Neurofilament protein (NFP), a neuronal cytoskeletal protein, is immunohistochemically recognized in only a part of neurons, apparently due to the scarcity in neurofilaments in some neurons or to a decreased antigenicity for NFP in the cell. Similarly, only small populations of cells in restricted types of paraneurons, including gut endocrine cells and thyroid C cells, are immunoreactive for NFP. However, the potentiality for paraneurons to express NFP is given credence by the fact that its immunoreactivity is rather frequently found in the neoplasmas of paraneurons which normally do not show this immunoreactivity. Spot 35 protein which is a cerebellar Purkinje cell-specific protein, has displayed immunohistochemical localization in sensory and endocrine paraneurons as well as some neurons including a specific type of intramural nerve cells in the gut. The selective localization of this calcium-binding protein may be correlated with the secretory function and calcium-dependent excitable membrane property in those cells. S-100 protein, another brain-derived calcium-binding protein, is contained in sustentacular cells of paraneuronal organs as well as glial elements of nervous systems. Although it is now widely accepted that S-100 protein is not "glia-specific" but contained in a variety of non-glial cells, its beta subunit protein is still a useful marker for a series of glial and sustentacular cells.