Inflammation and age-related iron accumulation in F344 rats.
Evidence suggests chronic inflammation and iron accumulation may play a role in the pathogenesis of Parkinson's disease (PD) as inflammation and iron levels increase with age and appear in the disease pathology. It is hypothesized that an aggravated inflammatory response and iron accumulation, as a function of age, increase oxidative stress and participate in the pathogenesis of PD. Intracranial injection of the bacterial endotoxin, lipopolysaccharide (LPS), has been shown to induce microglia activation, oxidative stress, mitochondrial impairment, iron accumulation, and dopaminergic neurodegeneration within the substantia nigra. We tested the hypothesis that injection of LPS into the striatum would increase iron accumulation in the substantia nigra of aged rats compared to young ones. Our results showed that four weeks post injection, LPS significantly increased microglia activation, lipid peroxidation, ferritin expression, and total nigral iron content in aged rats. In addition, LPS significantly altered the turnover ratio of homovanillic acid to dopamine. Thus, an age-related increase in iron as well as susceptibility to inflammation may play an important role in PD-related neurodegeneration, as free radicals produced from the inflammatory response can become more toxic through increased ferrous iron catalyzed Fenton chemistry. This may enhance oxidative stress, exacerbate microglia activation, and drive the progression of PD.
Hunter
Randy L
RL
Department of Anatomy and Neurobiology, University of Kentucky, Lexington KY 40536-0098, USA.
Liu
Mei
M
Choi
Dong Young
DY
Cass
Wayne A
WA
Bing
Guoying
G
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004731:Endotoxins; D005293:Ferritins / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009836:Oligodendroglia / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology
D004731:Endotoxins; C027952:salmonella toxin; D005293:Ferritins; D007501:Iron; D004298:Dopamine; D006719:Homovanillic Acid