Effects of dietary restriction and metal supplementation on the accumulation of iron-laden glial inclusions in the aging rat hippocampus

The mechanisms responsible for the pathological deposition of iron and other redox-active metals in the aging and degenerating mammalian CNS remain poorly understood. We previously demonstrated that normal aging and pharmacological ( oxidative) stressors promote the transformation of astroglial mitochondria to iron-laden, diaminobenzidine (DAB)-positive cytoplasmic inclusions in sub-cortical regions of the rat brain. In the current study, we demonstrate that ( 1) numbers of DAB-positive glial granules in the rat dorsal hippocampus, an area implicated in learning and memory, progressively increase between 3, 12 and 22 months of age; ( 2) dietary restriction (40%), a manipulation that attenuates many mammalian aging processes, has no effect on the age-related accumulation of these gliosomes in the rat hippocampus; and ( 3) the latter can be accelerated by dietary supplementation of iron and copper. Our data support the view that dietary exposure to iron and/or copper in adult life can impact the sequestration of redox-active metals in aging hippocampal astroglia.