Neuronal degeneration by suicide transport following injection of volkensin into rat cerebral cortex

We have examined the time course of neurodegeneration in subcortical nuclei and other cortical areas known to project to the rat parietal cortex, following unilateral injection of the suicide transport agent, volkensin, into the cortex of one side. Degenerating neurons, visualized by Gallyas silver staining were most prominent 21 days after injection. At this time darkly staining neurons were present in nuclei and areas known to project to the injected cortical area but not in other sites. Affected subcortical nuclei included the ipsilateral ventral thalamus and intralaminar nuclei, the basal nucleus of Meynert and claustrum 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 side. The distribution of degenerating cells is in agreement with the conclusion that only neurons projecting to the injection site were affected. The time course of the appearance of the degeneration and its distribution are in keeping with axonal transport rather than spread by diffusion of the toxin. Neuronal counts in Nissl-stained sections of the contralateral SMI confirmed significant neuronal loss 28 days after injection. In situ hybridization studies using an oligonucleotide probe directed against GAD mRNA and counts of GAD mRNA-positive neurons in the contralateral cortex confirmed that this population of cortical interneurons, which do not project to the injection site, were unaffected. (C) 1997 Academic Press.