Lactoferrin is synthesized by mouse brain tissue and its expression is enhanced after MPTP treatment

The presence of iron in brain tissue in increased concentrations in Parkins on's disease cases, where it might be responsible for oxidative stress, and the parallel observation that the iron transporter lactoferrin (Lf) was pr esent in increased amounts in surviving neurons, led us to study the synthe sis of Lf in a mouse model of Parkinson's disease. In this context, the ori gin and expression of brain Lf in normal, aged and MPTP (1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine)-treated mice were investigated. Lf immunostaini ng was observed mainly on microvessels in the cerebral cortex of the adult mice and to a greater extent in older mice. Lf immunoreactivity was also pr esent in the hippocampus only in the aged mouse brains, associated with str uctures which seemed to be pyramidal neurons and fibers. After RT-PCR (poly merase chain reaction), Lf transcripts were found in mouse brain tissue wha tever the age of the animals studied but the level of their expression was very low. No up-regulation of Lf was detectable during aging. Lf distributi on and expression in the MPTP-induced Parkinsonian mouse model were also in vestigated. A marked depletion of dopamine (DA) occurred in the high dose M PTP-treated mice. The level of Lf expression was found to be markedly incre ased in the same animals and this up-regulation occurred on the first day a fter MPTP administration. When the brain was stressed by the neurotoxin MPT P, Lf expression increased in line with antioxidant enzymes such as catalas e and gamma-glutamylcysteine synthetase, which may permit the protection of brain tissue from oxidative damage induced by the drug. (C) 1999 Elsevier Science B.V. All rights reserved.