Experimental induction of corpora amylacea in adult rat brain.
Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.
Schipper
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Bloomfield Centre for Research in Aging, Sir Mortimer B. Davis-Jewish General Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001923:Brain Chemistry / Q000187:drug effects; D002478:Cells, Cultured; D003543:Cysteamine / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014452:Ubiquitins / Q000032:analysis
D005904:Glial Fibrillary Acidic Protein; D014452:Ubiquitins; D003543:Cysteamine