Amyloid-beta transporter expression at the choroid plexus in normal aging: the possibility of reduced resistance to oxidative stress insults.
Accumulation of amyloid-beta peptides (Aβ) results in amyloid burden in normal aging brain. Clearance of this peptide from the brain occurs via active transport at the interfaces separating the central nervous system (CNS) from the peripheral circulation. The present study was to investigate the change of Aβ transporters expression at the choroid plexus (CP) in normal aging. Morphological modifications of CP were observed by transmission electron microscope. Real-time RT-PCR was used to measure mRNA expressions of Aβ(42) and its transporters, which include low density lipoprotein receptor-related protein-1 and 2 (LRP-1 and -2), P-glycoprotein (P-gp) and the receptor for advanced glycation end-products (RAGE), at the CP epithelium in rats at ages of 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33 and 36 months. At the same time, the mRNA expressions of oxidative stress-related proteins were also measured. The results showed that a striking deterioration of the CP epithelial cells and increased Aβ(42) mRNA expression were observed in aged rats, and there was a decrease in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE mRNA expression and an increase in LRP-2, the CP epithelium Aβ influx transporter. Heme oxygenase-1 (HO-1) and caspase-3 expressions at the CP epithelium increased with age at the mRNA level. These results suggest the efficacy of the CP in clearing of Aβ deceases in normal aging, which results in the increase of brain Aβ accumulation. And excess Aβ interferes with oxidative phosphorylation, leads to oxidative stress and morphological structural changes. This in turn induces further pathological cascades of toxicity, inflammation and neurodegeneration process.
Departments of Physiology and Pharmacology, School of Medicine, Huzhou Teachers College, Huzhou 313000, China; Department of Physiology, Wenzhou Medical University, Wenzhou 325000, China. liuchongbin1972@126.com.
Chong-Bin
CB
Liu
Rui
R
Wang
Miao-Wu
MW
Dong
Xi-Ren
XR
Gao
Feng
F
Yu
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002831:Choroid Plexus / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D016229:Amyloid beta-Peptides; D026502:LDL-Receptor Related Proteins; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3