NEURONAL DEGENERATION BY SUICIDE TRANSPORT FOLLOWING INJECTION OF VOLKENSIN INTO RAT CEREBRAL-CORTEX

We have examined the time course of neurodegeneration in subcortical n uclei and other cortical areas known to project to the rat parietal co rtex, following unilateral injection of the suicide transport agent, v olkensin, into the cortex of one side. Degenerating neurons, visualize d by Gallyas silver staining were most prominent 21 days after injecti on. At this time darkly staining neurons were present in nuclei and ar eas known to project to the injected cortical area but not in other si tes. Affected subcortical nuclei included the ipsilateral ventral thal amus and intralaminar nuclei, the basal nucleus of Meynert and claustr um of the same side, and the dorsal median raphe nucleus of both sides . Within the cortex degenerating pyramidal neurons were visible in the contralateral parietal cortex and in the frontal cortex of the same s ide. The distribution of degenerating cells is in agreement with the c onclusion that only neurons projecting to the injection site were affe cted. The time course of the appearance of the degeneration and its di stribution are in keeping with axonal transport rather than spread by diffusion of the toxin. Neuronal counts in Nissl-stained sections of t he contralateral SMI confirmed significant neuronal loss 28 days after injection. In situ hybridization studies using an oligonucleotide pro be directed against GAD mRNA and counts of GAD mRNA-positive neurons i n the contralateral cortex confirmed that this population of cortical interneurons, which do not project to the injection site, were unaffec ted. (C) 1997 Academic Press.