Anti-ubiquitin immunoreactivity associates with pyramidal cell death induced by intraventricular infusion of leupeptin in rat hippocampus.
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.
Okada
M
M
Division of Discovery Research Laboratories II, Shionogi Research Laboratories, Shionogi & Co. Ltd., Osaka, Japan.
Miyake
T
T
Kitamura
T
T
Kawasaki
K
K
Mizushima
Y
Y
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*
D007976:Leupeptins; D014452:Ubiquitins; C032854:leupeptin