The microsomal calcium-ATPase inhibitor thapsigargin is a neurotoxin in perinatal rodent brain.
Thapsigargin is a potent inhibitor of the microsomal calcium-ATPase. We hypothesized that thapsigargin-induced liberation of calcium from sequestered intracellular sites could result in irreversible brain injury. To assess neurotoxicity, intracerebral injections of 0.1-100 nmol thapsigargin were performed in 7-day-old rats, and the severity of injury was assessed 5 days later by microscopy and measurements of lesioned areas. We found that thapsigargin elicited dose-dependent tissue injury in perinatal rodent brain.
Silverstein
F S
FS
Department of Pediatrics, University of Michigan, Ann Arbor 48109.
Nelson
C
C
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000473:pathology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D007267:Injections; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000008:administration & dosage / Q000633:toxicity*; D019284:Thapsigargin
D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases