The turnover of myelin phospholipids in the adult and developing rat brain

Abstract

1. Inorganic [(32)P]phosphate, [U-(14)C]glycerol and [2-(14)C]ethanolamine were injected into the lateral ventricles in the brains of adult rats, and the labelling of individual phospholipids was followed over 2-4 months in both a microsomal and a highly purified myelin fraction. 2. All the phospholipids in myelin became appreciably labelled, although initially the specific radioactivities of the microsomal phospholipids were somewhat higher. Eventually the specific radioactivities in microsomal and myelin phospholipids fell rapidly at a rate corresponding to the decline of radioactivity in the acid-soluble pools. 3. Equivalent experiments carried out in developing rats with [(32)P]phosphate administered at the start of myelination showed some persistence of phospholipid labelling in the myelin, but this could partly be attributed to the greater retention of (32)P in the acid-soluble phosphorus pool and recycling. 4. It is concluded that a substantial part of the phospholipid molecules in adult myelin membranes is readily exchangeable, although a small pool of slowly exchangeable material also exists. 5. A slow incorporation into or loss of labelled precursor from myelin phospholipids does not necessarily give a good indication of the rate of renewal of the molecules in the membrane. As presumably such labelled molecules originate by exchange with those in another membrane site (not necessarily where synthesis occurs) it is only possible to calculate the turnover rate in the myelin membrane if the behaviour of the specific radioactivity with time of the phospholipid molecules in the immediate precursor pool is known.

Substrate-Reduction Therapy Enhances the Benefits of Bone Marrow Transplantation in Young Mice with Globoid Cell Leukodystrophy

“…In an earlier study that treated twitcher mice only with L-cycloserine, the beneficial effects were observed when treatment was started at postnatal d 4 -5 but not for treatment started at postnatal d 21-22 (39). The explanation for this time constraint was that the galactosylceramide that was scheduled to be recycled already had been synthesized before the initiation of the late administration of L-cycloserine as the turnover rate of myelin is slow (47)(48)(49). Thus, in the present study, BMT slowed the disease enough to permit a late regimen of L-cycloserine to contribute to the beneficial effects of the combination therapy.…”

L-cycloserine slows the clinical and pathological course in mice with globoid cell leukodystrophy (twitcher mice)

“…L-cycloserine administration starting at this time is believed to have no effect, since much of the galactosylcer- amide that is scheduled to be recycled has been previously synthesized (Smith, 1968) due to the slow turnover rate of myelin (Jungalwala and Dawson, 1971;Jungalwala, 1974). Since disease in twitcher mice is comparable to the infant onset form of disease in humans, which has a rapid downhill course, there probably isn't enough time for the late administration of L-cycloserine to have any therapeutic value.…”

Étude comparative de la biosynthèse des phosphatidylcholines dans les neurones et les cellules gliales du cerveau de poulet

“…La capaciti de synthkse des licithines du riticulum endoplasmique de chaque type cellulaire &ant similaire telle qu'elle apparal" g la lumi&e de la mesure de l'activit8 de la phosphocholine diglyceride transfkase, suggkre que le renouvellement des phosphatidylcholines des neurones est plus intense que celui des cellules gliales, ce dernier type cellulaire accusant un taux de lkcithine 5 fois supkrieur ?I celui des neurones et Qtant Bgalement le lieu de synth&e des compos& des gaines de myCline [ 16,171. LJne telle hypoth&e est en accord avec nos rksultats anterieurs montrant que les demi-vies des phosphatidylcholines des neurones sont plus courtes que celles des composes correspondants des cellules gliales [ 181.…”