STATHMIN - CELLULAR-LOCALIZATION OF A MAJOR PHOSPHOPROTEIN IN THE ADULT-RAT AND HUMAN CNS

Stathmin is a ubiquitous, 19 kDa cytoplasmic protein the phosphorylati on of which is associated with many cellular signaling pathways. It is particularly abundant in neurons and reaches a peak of expression in the neonatal period, although it remains highly expressed in the adult brain. In order to determine whether this abundant expression is asso ciated with discrete cellular populations that are still at an immatur e stage during adulthood, as suggested by others, the cellular localiz ation of stathmin was investigated in the adult rat and human central nervous system. Western blotting with a specific antiserum indicated t hat stathmin was ubiquitous in the brain and spinal cord but that its relative concentration varied up to 2.6 times between regions. To char acterize the distribution of stathmin within the brain, its cellular l ocalization was analyzed by immunocytochemistry. Highly immunoreactive neurons and oligodendrocytes were observed, and stathmin immunoreacti vity was localized to the perikaryon and all processes, but not the nu cleus. Most brain and spinal cord cell groups showed stathmin immunore activity, although the extent and intensity of labeling differed large ly from one place to another. Particularly numerous stathmin-immunorea ctive neuronal cell bodies were found in the pyriform, cingulate, and neocortex, as well as in many cholinergic nuclei of the basal forebrai n and brainstem, in the medial thalamus, in various brainstem nuclei, in the dorsalmost layers of the spinal cord, and in brain areas lackin g a blood-brain barrier to macromolecules. In addition to neuronal pop ulations, stathmin-antibodies intensely labeled choroid plexuses. Many other brain regions exhibited moderate neuronal immunostaining. The d istribution of stathmin-immunoreactive processes was in some areas rel atively heterogeneous. Intense immunoreactivity was observed in some f iber tracts (corpus callosum, anterior commissure, inferior cerebellar peduncle, etc.) but was missing in others (internal capsule, posterio r commissure, etc.). Some brain areas rich in immunoreactive neurons a lso displayed an intense immunoreactivity of the neuropile, whereas ot hers contained either immunoreactive cells or fibers. In the human bra in, stathmin immunostaining occurred in many areas, corresponding to t hose identified in the rat, with the exception of the cerebral cortex, the hippocampal fascia dentata, and the substantia nigra. The present results support our suggestion that, in addition to its involvement i n cell proliferation and differentiation, stathmin may also be related to regulation of differentiated cell functions, as it appears to be a major signaling protein in widespread areas of the adult brain in bot h rat and human. (C) 1993 Wiley-Liss, Inc.