The progression of neuronal, myelin, astrocytic, and immunological changes in the rat brain following exposure to aurothioglucose.
Aurothioglucose (ATG) is presently employed both by clinicians in the treatment of advanced rheumatoid arthritis and by neuroscience researchers to generate lesions around the circumventricular organs (CVOs) of rodent brains, resulting in obese animals. Although the existence of such lesions is well documented, there is relatively little information concerning the changes over time of the different cell types in the regions surrounding the CVOs. To address this question, specific markers allowing identification of four distinct cellular populations were used to characterize respective changes over time. Generally, regions adjacent to the CVOs were more vulnerable than the CVOs themselves, while more caudal structures were more frequently lesioned than more anterior CVO regions. Vascular and glial cells appeared to be the initial targets of ATG, while neuronal cell death occurred subsequent to the inflammatory response. The results of this study help resolve the mechanism of ATG toxicity as reflected by a cascade of pathologies that is consistent with disparate cell types exhibiting specific changes at specific times.
Schmued
Larry C
LC
Department of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079, USA. lschmued@nctr.fda.gov
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D006051:Aurothioglucose / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000276:immunology; D007031:Hypothalamus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D006051:Aurothioglucose