Effects of cyclosporine-A on brain lipids and apolipoprotein E, J gene expression in rats.
Cyclosporine-A, an immunosuppressive agent, is known to produce complications such as seizures and encephalopathies. It alters peripheral lipid metabolism, but its effect on brain lipid metabolism is unknown. Alterations in brain cholesterol and phosphatidylcholine levels, as well as in apolipoproteine E and J gene expression, are reportedly involved in epilepsy and Alzheimer's disease (AD) and were here evaluated in rats following administration of cyclosporine-A for 3 weeks. Unesterified cholesterol and phospholipid brain levels were decreased by cyclosporine whereas apolipoprotein E and J mRNA levels were not altered in hippocampus or in cortex. These alterations in brain lipid metabolism are not similar to that reported in epilepsy or AD and exclude the involvement of apolipoprotein E and J over-expression in cyclosporine-mediated neurological disorders.
Montpied
Pascale
P
CNRS UMR 5094, Faculté de pharmacie, BP 14491, av Charles Flahaut, 34093, Montpellier cedex 5, France. pascale.montpied@ibph.phama.univ-montpl.fr
Batxelli
Isabelle
I
André
Marc
M
Portugal
Henri
H
Lairon
Denis
D
Bockaërt
Joël
J
Chanussot
Françoise
F
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D051152:Clusterin; D016572:Cyclosporine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000145:classification; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D001057:Apolipoproteins E; D051152:Clusterin; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008055:Lipids; D018832:Molecular Chaperones; D012333:RNA, Messenger; D016572:Cyclosporine; D002784:Cholesterol