Induction of age pigment accumulation in the brain cells of young male rats through iron-injection into the cerebrospinal fluid.
The OH free radical formation can be increased in the brain by intralumbar iron injections into the cerebrospinal fluid (CSF) through the Fenton reaction. Ferrous ammonium sulphate was injected to male CFY rats of 3 months of age. The animals survived a single dose of 4 mumoles, and this treatment was repeated daily for 3 or 6 days. The total iron contents of the large brain and the cerebellum were measured by atomic absorption spectroscopy; 3 days of iron administration resulted in significant increases of iron contents only in the cerebellum, whereas after 6 days, both parts of the brain showed considerably higher iron contents. Electron microscopic point-counting morphometric analysis revealed a 65% increase of volume density of the lipofuscin in the large cells of parietal cortex after 6 days of iron-treatment. The Purkinje cells displayed a particularly frequent occurrence of an "apoptosis"-like structural alteration under the effect of iron. This kind of experimental approach is complicated by the facts that (i) the increase of OH radical flux above a certain level is lethal, and (ii) the young animals have a very active elimination mechanism of the waste products. Nevertheless, the enhancement of OH radical yield by an increased availability of iron for Fenton reaction resulted in an accumulation of lipofuscin even in young rats.
Zs-Nagy
I
I
F. Verzár International Laboratory for Experimental Gerontology, University Medical School, Debrecen, Hungary.
Steiber
J
J
Jeney
F
F
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008062:Lipofuscin / Q000032:analysis* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005296:Ferrous Compounds; D008062:Lipofuscin; D000644:Quaternary Ammonium Compounds; C038178:ammonium ferrous sulfate