dolichols and Nerve-Degeneration

During aging the human brain shows a progressive increase in levels of dolichol, a reduction in levels of ubiquinone, but relatively unchanged concentrations of cholesterol and dolichyl phosphate. In a neurodegenerative disease, Alzheimer's disease, the situation is reversed with decreased levels of dolichol and increased levels of ubiquinone. The concentrations of dolichyl phosphate are also increased, while cholesterol remains unchanged. This study shows that the isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging and that this disease cannot, therefore, be regarded as a result of premature aging. The increase in the sugar carrier dolichyl phosphate may reflect an increased rate of glycosylation in the diseased brain and the increase in the endogenous anti-oxidant ubiquinone an attempt to protect the brain from oxidative stress, for instance induced by lipid peroxidation.

Topics: Adult; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Animals; Brain Chemistry; Cells, Cultured; Cholesterol; Dolichol Phosphates; Dolichols; Humans; Lipid Metabolism; Mevalonic Acid; Middle Aged; Nerve Degeneration; Polyisoprenyl Phosphates; Rats; Ubiquinone

Cultured neurons from rat dorsal root ganglia and cerebral cortex were infected with Sendai virus, which gives a productive replication with lysis of most neurons, and with the RW strain of mumps virus, which undergoes defective replication causing degeneration of only 30-40% of the neurons within 5 days after initial infection. In Sendai virus-infected cells the amount of polyisoprenoid lipids was enhanced. In mumps virus-infected cultures there were transient reductions in the contents of cholesterol, dolichol, and ubiquinone-9 in the cultures, whereas the reduction in the ubiquinone-10 level was progressive, reaching 20% of its original value 21 days after infection. Treatment of mumps virus-infected cultures with ubiquinone-10 protected the neurons from degeneration, whereas no effects were observed on exposure to ubiquinone-9. Linolenic acid (18:3) and arachidonic acid (20:4), but not myristic acid (14:0) and palmitic acid (16:0), also had significant neuroprotective effects.

Topics: Animals; Cell Survival; Cells, Cultured; Cerebral Cortex; Cholesterol; Dolichols; Fatty Acids, Nonesterified; Ganglia, Spinal; Kinetics; Mumps virus; Nerve Degeneration; Neurons; Parainfluenza Virus 1, Human; Peroxides; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; tert-Butylhydroperoxide; Time Factors; Ubiquinone; Virus Replication