Early Stages Of Myelination Research Articles

Protein determinants of myelination in different regions of developing rat central nervous system

Measurements of several different protein determinants correlated with the time and rate of myelination in five areas of the central nervous system are presented. The deposition of protein in the subcellular fraction corresponding to the density of adult myelin, the appearance of basic protein characteristic myelin, the change in proportions of the individual myelin proteins, the appearance and distribution of the myelin marker 2':3'-cyclic nucleotide3'-phosphohydrolase, and the results of morphological studies of purified myelin are compared. According to these various criteria, and in agreement with the morphological observations of others, myelin appears earliest in the spinal cord, then in the brain stem, and latest in the cerebral hemispheres. Multilamellar myelin was observed in the rat brain stem and spinal cord as early as 5 days of age. The relative proportion of the individual myelin proteins changed with myelin maturation in all areas, with the larger basic protein decreasing reciprocally with increase of the smaller basic protein. The proportion of Wolfgram protein also decreased with maturation. Larger proportions of the enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase were located in the microsomal fraction at early ages. During development the enzyme activity gradually became associated more with a fraction of a density corresponding to adult myelin, suggesting the presence of precursor membrane fragments in microsomal fractions in the early stages of myelination before compact myelin formation. A significant proportion of the total nucleotide phosphohydrolase activity of the homogenate could not be recovered in subcellular fraction at early ages, but the recovers of the enzyme increased with maturation and the activity was found more in the myelin fraction.

Jimpy, an anomaly of myelin maturation. Biochemical study of myelination phases

Development changes in brain composition during myelination were studied in a myelin-deficient mutant, the Jimpy mouse. The brain composition showed practically an absence of accumulation during development of myelin basic proteins, cerebroside and sulfatide. The sequence of maximum rates of accumulation indicated that the first phase of myelination, which represents oligodendrocyte proliferation and early myelin formation, was unaffected by the mutation. In contrast, the second phase, the phase of compact myelin sheath formation, was practically missing. These findings seem to indicate an arrest of differentiation at an early stage of myelination.

Composition of cerebral lipids in murine leucodystrophy: the quaking mutant.

Abstract—The composition of sphingolipids and phospholipids of mouse brain during myelination was determined in the Quaking mutant, which manifests a genetic disorder of myelin formation, and in littermate controls. The biochemical changes during myelination in the brains of the controls corresponded quantitatively with previous findings in a different strain of mice. The Quaking mutant exhibited concentrations of sphingolipids and phospholipids in brain which were comparable to those of controls in the early stage of myelination but the tissue content failed to increase with maturation. The greatest differences occurred in the cerebrosides which at 65 days of postnatal age were only 10 per cent of control levels. During development the pattern of cerebral levels of sphingomyelin, plasmalogen and total phospholipid in the mutants tended to resemble that of the cerebrosides.The defect in the Quaking mutant is compatible with a failure in maturation of myelin. These findings have been compared with those in the Jimpy mutant, a different genetic disorder of myelin in the mouse previously studied in a similar fashion. The Jimpy mutant is characterized by a quantitatively more pronounced deficiency of myelin lipids and a decline in cerebrosides during brain development.

TRIPHOSPHOINOSITIDE PHOSPHODIESTERASE IN DEVELOPING BRAIN OF THE RAT AND IN SUBCELLULAR FRACTIONS OF BRAIN

Abstract— An assay system for the measurement of triphosphoinositide phosphodiesterase in homogenates of rat brain is described. With triphosphoinositide (TPI) as substrate, and in the presence of 0·1 m‐KCI and saturating amounts of diethyl ether, the activity of phosphodiesterase in myelinated brain was 400–500 μmoles of TPI hydrolysed per g wet wt. per hr. One quarter of the adult level of the enzyme was present in rat brain one day after birth, with the remainder being added prior to and during the early stages of myelination. On subfractionation of brain homogenates, substantial activity of the enzyme was located in the soluble portion and in the paniculate fractions enriched in myelin and synaptosomes. The enzyme associated with the particulate fractions could not be detached from the membranes by any of several methods employed. There was a rough correlation between distribution of phosphodiesterase and that of 5′‐nucleotidase, an enzyme associated with plasma membrane in a number of tissues. Some implications of the results are discussed.

An electron microscopic study of the neuroglia during postnatal development of the rat cerebrum.

AbstractThe differentiation of spongioblasts from undifferentiated cells and into neuroglial cells has been studied in the postnatal rat cerebral cortex with the electron microscope. The nuclei of all the non‐neural elements are characterized by clumping of dense chromatin, especially near the nuclear envelope. The undifferentiated cells possess only a thin rim of perinuclear cytoplasm containing few organelles. Spongioblasts are characterized by an increased number of cytoplasmic organelles, mostly mitochondria and Golgi complex, and by the growth of processes. These cells mature and take on either the features of oligodendrocytes or astrocytes. The multiple oligodendrocyte processes are thin and branching and develop intimate contacts with the developing axons. Early stages of myelination are characterized by the envelopment of axons by oligodendrocyte processes which overlap each other to form inner and outer tongues that are cheracteristic of central nervous system myelin. Astrocytes can be distinguished by the presence of cytoplasmic glycogen particles and fibrils. Processes of these latter cells develop intimate relations with the developing blood vessels. A variety of cell was occasionally encountered which is termed the polycystic cell. This cell may be quite large, contains numerous cysts and vesicles of various types and appears to be a form of spongioblast. No cells which would qualify as “microglia” were observed.