Immunization with cholinergic cell bodies induces histopathological changes in rat brains

Abstract

We have previously shown that sera from patients with Alzheimer's disease (AD) contain antibodies to the cell bodies (perikarya; PK) of purely cholinergic Torpedo neurons, and that repeated immunization of rats with this neuronal preparation for over a year induces learning and memory impairments. In the present study, we examined the brain morphology of cholinergic PK immunized rats relative to controls. Immunohistochemical studies of the brains of these rats revealed the accumulation of IgG in specific areas, such as, the hippocampus. Parallel histochemical studies demonstrated significant changes in the hippocampus, and in white matter areas. They included large vacuoles and necrotic nuclei in the granular layer of the dentate gyrus, tangle-like appearance in some pyramidal neurons of the hippocampus, and vacuolar degeneration accompanied by oligodendroglia hypertrophy in white matter tracts, such as, the corpus callosum and fimbria. In contrast, immunization with Torpedo cholinergic nerve terminals, that has no cognitive effects on the rat, also did not induce brain morphological changes. These findings suggest that the learning and memory deficits induced by immunizing rats with cholinergic PK are related to the observed brain morphological changes, and support the hypothesis that the antibodies to cholinergic neurons found in the sera of AD patients may play a role in neuronal degeneration in this disease.

Genetic evidence for pax‐3 function in myogenesis in the nematode Pristionchus pacificus

“…Most prominently, only one homolog of MRFs has been identified in C. elegans and other invertebrates, whereas vertebrates have four MRF encoding genes. hlh‐1 in C. elegans (Krause et al 1990), nau in D. melanogaster (Michaelson et al 1990; Paterson et al 1991), sum‐1 in sea urchins (Venuti et al 1991), and amd‐1 in the ascidian, H. roretzi (Araki et al 1994) all represent single copy genes. While a subset of MRFs appears to be both necessary and sufficient for vertebrate skeletal myogenesis, mutants lacking the single MRF‐related factor nau or hlh‐1/CeMyoD are still able to specify and differentiate striated muscle (Chen et al 1992; Balagopalan et al 2001).…”