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Abstract

Turnover rates of myelin membrane components in mouse brains were determined by a method using stable isotope-labeling and mass spectrometry. The half-replacement times based on incorporation rates of newly synthesized molecules for young adult mice were 359 days for cholesterol, 20 days for phosphatidylcholine, 25 days for phosphatidylethanolamine, 94 days for cerebroside and 102 days for ganglioside GM1. The turnover rates of half-lives of myelin components were calculated from the decay curves of initially labeled molecules, and they were about the same as the half-replacement times. Individual components were thus revealed to be metabolized at different rates, and their turnover rates were differently affected by aging. As was observed with phospholipids, myelin pools appeared to be compartmentalized into rapidly and slowly exchanging pools. The turnover rates of cerebroside and GM1 decreased between the young and adult periods and slightly increased in senescence. The latter phenomenon may indicate an enhanced myelin turnover in senescence. The present study reveals the dynamic aspects of myelin membrane turnover during the life span of mouse.

Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology

“…However, a possible explanation may relate to the half life for myelin related proteins, which in animals has been determined to be in the same approximate time frame as the clinic deterioration seen in these cases of DPHLE (Figure 4; mean time for lucid interval: 19 days). A study by Ando et al 12 . found that the half-replacement times as judged by newly synthesized molecule incorporation rate in young adult mice was 20 days for phosphatidylcholine, 25 days for phosphatidylethanolamine.…”

Studies on the Transcriptional Regulation of Cholesterol 24-Hydroxylase (CYP46A1)

“…myelin), with a half-life of ϳ1 year in mice (38). The stability of brain cholesterol is further highlighted by the fact that overall CNS cholesterol concentration is unchanged in animal models where genes known to be involved in cholesterol transport are inactivated.…”

Myelination and mTOR

“…More recently, isotope labeling and mass spectrometry have been employed to overcome these pitfalls. Using a pulse of deuterated water, the half‐lives of myelin lipids were estimated to range from 360 days for cholesterol to 24 days for phosphatidylcholine (Ando, Tanaka, Toyoda, & Kon, 2003). Following an analogous approach in which proteins were pulse‐labeled with 15 N followed by a chase period with 14 N, the myelin proteins myelin basic protein (MBP), proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), and 2′,3′‐cyclic‐nucleotide 3′‐phosphodiesterase (CNP) were identified in an unbiased manner among the long‐lived proteins of the brain (Toyama et al, 2013).…”