volkensin and Disease-Models--Animal

Retrogradely transported toxins are widely used to set up protocols for selective lesioning of the nervous system. These methods could be collectively named "molecular neurosurgery" because they are able to destroy specific types of neurons by using targeted neurotoxins. Lectins such as ricin, volkensin, or modeccin and neuropeptide- or antibody-conjugated saporin represent the most effective toxins used for neuronal lesioning. Some of these specific neurotoxins could be used to induce selective depletion of spinal motoneurons. In this review, we extensively describe two rodent models of motoneuron degeneration induced by volkensin or cholera toxin-B saporin. In particular, we focus on the possible experimental use of these models to mimic neurodegenerative diseases, to dissect the molecular mechanisms of neuroplastic changes underlying the spontaneous functional recovery after motoneuron death, and finally to test different strategies of neural repair. The potential clinical applications of these approaches are also discussed.

Topics: Animals; Cholera Toxin; Disease Models, Animal; Nerve Degeneration; Nerve Regeneration; Neuronal Plasticity; Rats; Ribosome Inactivating Proteins, Type 1; Ribosome Inactivating Proteins, Type 2; Saporins

Pyramidal neurones of the neocortex have been implicated in a number of neuropsychiatric diseases, such as Alzheimer's disease. Markers that may identify these cells have been investigated using a novel technique. A subpopulation of corticifugal neocortical pyramidal neurones was destroyed by the unilateral striatal injection of volkensin, a toxin that undergoes retrograde suicide transport from the site of injection. Striatal volkensin injections produced significant reductions in the number of large pyramidal neurones of the infragranular cortical layer. The selectivity of the lesion was demonstrated by the preservation of cells containing glutamic acid decarboxylase mRNA, which are considered to be cortical interneurones. Ricin, another toxic lectin, but effective as a suicide transport agent exclusively in the PNS, produced local striatal damage but no cortical cell loss. In autoradiographic binding studies of animals treated with volkensin, binding in deep neocortical layers of [3H]8-hydroxy-2-(n-dipropylamino) tetralin ([3H]8-OH-DPAT) to 5-HT1A but not of [3H]ketanserin to 5-HT2 receptors was significantly reduced. The N-methyl-D-aspartate receptor complex was investigated using the novel glycine site antagonist [3H]L-689,560, and the muscarinic M1 receptor using [3H]pirenzepine. Significant reductions in binding of [3H]L-689,560 and [3H]pirenzepine were observed in the deep neocortical layers of the animals that had been injected with volkensin. The rank order of the ligands as effective markers for this subpopulation of pyramidal neurones was [3H]8-OH-DPAT >> [3H]pirenzepine > [3H]L-689,560 >> [3H]ketanserin. These findings are thought to have advanced the understanding of the biology of pyramidal neurones. Implications for in vivo imaging treatment of neuropsychiatric conditions such as Alzheimer's disease are discussed.

Topics: Alzheimer Disease; Animals; Autoradiography; Cell Death; Disease Models, Animal; Glycoproteins; Injections; N-Glycosyl Hydrolases; Neurons; Plant Lectins; Plant Proteins; Pyramidal Tracts; Rats; Rats, Sprague-Dawley; Receptors, Neurotransmitter; Receptors, Serotonin; Ribosome Inactivating Proteins, Type 2; Toxins, Biological