title: Anti-ubiquitin immunoreactivity associates with pyramidal cell death induced by intraventricular infusion of leupeptin in rat hippocampus.
abstract: Pathological studies on several neurodegenerative diseases including Alzheimer's disease have revealed common deposition of ubiquitin in many inclusion bodies. This implies a possible association of ubiquitin with neurodegeneration. To address this possibility, we examined histochemically the effect of intraventricular infusion of leupeptin, a thiol proteinase inhibitor, which is known to elevate anti-ubiquitin immunoreactivity in rat Purkinje cells. In the leupeptin-infused rat, an intense anti-ubiquitin immunoreactivity in the cytoplasm of neurons occurred not only in cerebellar Purkinje cells but also elsewhere in a wide area of the rat brain. The increase in the immunoreactivity was followed by a gradual depletion of pyramidal neurons in the hippocampal CA1 and CA3 subfields. The immunoreactive neurons disappeared concurrently. The number of anti-ubiquitin immunoreactive neurons was negatively correlated with that of surviving neurons when the duration of leupeptin infusion was varied. These results suggest that increased anti-ubiquitin immunoreactivity associates with neuronal death in leupeptin-treated rat brain.
authors.affiliation: Division of Discovery Research Laboratories II, Shionogi Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Mizushima
mesh_terms: D000818:Animals; D016923:Cell Death; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D007976:Leupeptins; D014452:Ubiquitins; C032854:leupeptin