Cerebroside Content Research Articles

The role of dietary lactose in the synthesis of brain galactolipids

The brain is endowed with considerable autonomy in the synthesis of myelin lipids, several components of which can be made in 8itu, e.g. cholesterol, sphingosine and fatty acids. Myelination takes place at different stages of ontogenetic development, being virtually complete at birth in some species, or beginning only after birth in others. Cerebroside, one of the myelin lipids, appears relatively late in the phylogenetic evolution of the brain. None has been found in the central nervous system of some invertebrates (squid, arachnoid king crab, honey bee; McColl & Rossiter, 1950; Patterson, Dumm & Richards, 1945) and some of the positive reports of the occurrence of cerebrosides in crustaceans, fishes, amphibians, birds and even neonatal mammals are suspect on account of inadequate analytical techniques. Estimation of cerebrosides, based on determinations of total carbohydrate by relatively non-specific methods, often yields high results due, in part, to the presence of lipid-bound glycogen (S. N. Varma & V. Schwarz, unpublished work), gangliosides and possibly other glycolipids. Questionable as they are, the meagre data on the cerebroside content of the brain of different species suggest, however, that there is a gradual increase with evolution and ontogenetic development (Lanfranchi, 1938; McColl & Rossiter, 1952). The occurrence of lactose in the milk of all mammals examined so far has engendered speculation on a possible connexion between galactolipid synthesis and dietary galactose. Ziegler (1960) has drawn attention to a rough correlation between the lactose content of milk and the degree of brain development in different species. Thus human, horse and elephant milk has a lactose content of about 7%, cow, sheep and cat milk about 4.5%, and porpoise, guinea pig and rabbit milk about 2%. A crude proportionality between milk lactose and brain galactolipid has been observed by Sadhu (1948), who also found the cerebroside content of pigeon and rat brain to be increased after feeding with relatively large amounts of lactose. Of the two known galactose-containing families of lipids, gangliosides occur almost exclusively in the grey matter and (in man) are present at birth

Fatty acids of human brain cerebrosides

Four regions of two human brains were analyzed for the individual cerebroside acids: cerebral cortex white and gray matter, cerebellum (mainly gray matter), and corpus callosum. The total lipids were extracted from each section and passed through a column of Florisil to remove cholesterol and phosphatides. The crude cerebrosides were next passed through a column of mixed ion exchange resins to remove cerebroside sulfate and then purified by elution from a silicic-acid column. The acids were cleaved from the cerebrosides and separated into four classes: normal saturated, hydroxy saturated, normal unsaturated, and hydroxy unsaturated. The individual acids were then analyzed by gas-liquid chromatography. The cerebroside content of each brain region differed somewhat, as did the relative contents of hydroxy acids. However, the distribution of the acids within each class was rather independent of brain location. The normal saturated acids contained stearic and lignoceric as the major acids, but fairly large amounts of the C22, C23, and C25 acids were also present. The hydroxy saturated acids were similar, but contained little hydroxystearic acid. The unsaturated acids of both classes contained the C24, acid as the major constituent, together with considerable amounts of the C25 and C26 acids.

Determination of cerebrosides in different parts of the brain of rabbits suffering from generalized tetanus.

The cerebroside content of the subcortical formations of the cerebral hemispheres of rabbits falls following injection of a lethal dose of tetanus toxin into a hind leg to a minimum on the 7–8th day, when the animals are moribund. This effect is more pronounced in the hemisphere contralateral to the injection site.

ACUTE INFANTILE GAUCHER'S DISEASE

The present clinical conference takes up the case of a 5½-month-old boy who was admitted to the hospital because of irritability and failure to gain weight. His irritability progressed to definite neurologic signs, and marked enlargement of the spleen developed, together with some hepatomegaly. Bone marrow aspiration revealed abnormal cells, showing an eccentric nucleus and wavy, fibrillar cytoplasm, with an appearance consistent with Gaucher cells. A progressively downhill course ensued, characterized by opisthotonus and respiratory difficulties, and the child died at age 7 months. A discussion of numerous aspects of Gaucher's disease is presented, including biochemical and genetic considerations. The problems encountered in genetic counseling of parents who have children with this disease are brought out. Since Gaucher's disease as a syndrome exhibits a heterogenous pattern of inheritance, the dangers inherent in giving parents oversimplified genetic data are emphasized. If the parents ebect to have no further children of their own and instead wish to adopt children, certain implications which this course of action may raise are discussed. An experiment is described wherein spleen tissue obtained from two patients with Gaucher's disease was analyzed for cerebroside content. Most of the cerebroside found in both spleens was the abnormal glucose form, whereas in normal human tissue the galactose cerebroside predominates. Studies are being made in this laboratory of the incorporation of carbon-14 labelled glucose and galactose using microsomal fractions of spleens from patients with Gaucher's disease. On the basis of preliminary data, it is postulated that the site of the biochemical error in most patients with the disease is at the conversion of the glucocerebroside to the galactocerebroside. It is believed that a defect in a UDP-galactose-4-epimerase-like mechanism at this site would cause the accumulation of the "abnormal" glucose cerebroside. Figure 5 indicates graphically the location of this suggested metabolic block.

The lipophilic peptides and proteins of brain. III. Difference between brain and peripheral nerve

The respective neurosclerin contents of mouse, monkey, and cat brain were determined and compared with the amounts obtained from the sciatic nerve of the corresponding species. These values were related to the cerebroside content of the tissues. In all three species the neurosclerin content of brain exceeds that of the sciatic several fold, leading to widely divergent neurosclerin to cerebroside and neurosclerin to cholesterol ratios. In lobster leg nerves which lack myelin, the presence of a fraction homologous to the sciatic neurosclerin fraction was shown. The relationship of these findings to the proteolipids is discussed. It is suggested that neurosclerin probably represents a highly lipophilic membrane protein whose relationship to myelin proteins is as yet obscure.

A Comparative Study of the Lipids of the Vertebrate Central Nervous System

ABSTRACT The concentration of water, cerebroside (glycosphingoside), free and total cholesterol, total phospholipin, monoaminophospholipin (phosphoglyceride) and lecithin (phosphatidyl choline) was determined in the spinal cords of a series of vertebrates including representatives of the cartilaginous and bony fishes, amphibians, reptiles, birds and mammals. From these figures was calculatedthe concentration of ester cholesterol, sphingomyelin (phosphosphingoside) and kephalin. As was previously found for brain, the spinal cords of each of the species studied contained negligibly small concentrations of cholesterol ester. The concentration of each lipid in the spinal cord was very similar for different individuals of the same species, but for different species within the same class the mean concentration of many of the lipids extended over a wide range. The concentration of total cholesterol, sphingolipid and myelin lipid was greater in the spinal cords of mammals than in the spinal cords of the lower vertebrates. Expressed as a percentage of ‘essential lipid‘, the concentration of cerebroside, cholesterol, sphingomyelin, sphingolipid and myelin lipid, but not of lecithin and kephalin, was greater in the spinal cord than in the brain. For the spinal cords of the species studied, the mean concentration of cerebroside expressed as a percentage of ‘essential lipid’ was negatively correlated with the mean concentration of sphingomyelin. The results are discussed in relation to the chemical nature of the lipids of the myelin sheath of a vertebrate nerve fibre.

Role of fat on utilization of lactose in milk by rats and rabbits.

(1) The glycogen and fat contents of the liver are significantly diminished in the rats fed skim milk. (2) The cerebroside content of the brain of the skim milk-fed and whole milk—fed rats did not differ significantly. (3) Urinary excretion of galactose by the skim milk—fed rats might be due to non—conversion of galactose into glycogen in the liver. (4) The skim milk—fed rats utilized galactose to form cerebrosides of the brain and fat of the liver. (5) Unlike rats, rabbits fed skim milk for 2 months did not excrete galactose in urine.

LIPIDS OF THE NERVOUS SYSTEM DURINGIN VITRODEGENERATION

The changes in the concentration of lipids during the in vitro degeneration of cat brain slices and sciatic nerve have been determined after incubation in bicarbonate buffer for periods of time from 1 to 14 days. In brain slices incubated for 14 days there was a great decrease in the concentration of total phospholipid with no change in the concentration of cerebroside or total cholesterol. Of the individual phospholipids, there was a decrease in the concentration of sphingomyelin and cephalin and no significant change in the concentration of lecithin. In sciatic nerve incubated for eight days, there was a significant decrease in the concentration of cephalin and a decrease of borderline significance in the concentration of total phospholipid. There was no significant change in the concentration of cerebroside, free or total cholesterol, sphingomyelin, or lecithin. Thus in tissue of the nervous system, there appears to be a phospholipid-splitting mechanism, possibly enzymatic in nature.

魚類脳のコレステロール,隣脂體及びセレブロシツド含量に就いて

Cholesterol, phosphatide and cerebroside content of several fish braines were estimated. The results are shown in the following tables. The greater part of Cholesterol in fish braines exsts in free form but estered form is very small. (Table 1). The Cholesterol and phosphatide content of teleostbraines (12 samples) are selachians these content are less than teleosts. Cerebroside content of teleostbraines (3 samples) are 0.76-0.99% for fresh samples (Table 2).

Studies Concerning the Pathogenesis of Gaucher’s Disease

Abstract 1. The serum of normal individuals and of patients with Gaucher’s disease does not contain cerebrosides in measurable amounts. Cerebrosides in Gaucher’s disease are increased only in those organs containing abundant numbers of cells characteristic of the disease. 2. Normal red blood cells contain approximately 0.19 per cent cerebrosides. The cerebroside in red blood cells is a galactosidocerebroside. 3. Red blood cells in Gaucher’s disease do not differ quantitatively and qualitatively in their cerebroside content from the red blood cells of normal individuals. 4. In four different cases of Gaucher’s disease separate determinations of splenic galactosido- and glucosidocerebrosides were made. The spleen of two adults showed mainly glucosidocerebrosides and only traces of galactosidocerebrosides, while the analysis of the spleen of two other adults showed that galactosido- as well as glucosidocerebrosides may be accumulated simultaneously in Gaucher cells. These findings are of importance, since it is demonstrated that the deviation of the cerebroside metabolism in Gaucher cells not only results in the formation of an abnormal glucosidocerebroside, but also may lead to the increased formation of the normal galactosidocerebroside, kerasin. It is demonstrated that the relative proportions of galactosido- and glucosidocerebrosides in Gaucher cells may differ considerably in individual cases. 5. The organs of infantile siblings with "generalized infantile Gaucher’s" disease were analyzed. The organs of one infant showed mainly galactosidocerebrosides while in the organs of the other sibling both kinds of cerebrosides, glucosido- as well as galactosidocerebrosides, were present. 6. The findings reported in this paper lend support to the theory that Gaucher’s disease is the result of a deviation of the intracellular metabolism of reticulum cells and histiocytes. The cerebrosides are not transported by the serum or by the red blood cells and secondarily deposited in the cells involved, but are formed and stored in the reticulum cells and histiocytes were they are found.

Relation Between Cerebroside and Neutral Fat Contents of Blood Plasma, Erythrocytes and Stroma

That cerebrosides may exist in small amounts in blood has been shown by the development and application of a titrimetric microprocedure for this group of lipids.1, 2, 3 This method, slightly modified, has been employed on lipid extracts of blood, stroma and brain. The data indicate that in erythrocytes, stroma, and brain, much of the lipid which formerly was designated as neutral fat∗ is cerebroside, whereas in plasma only negligible amounts of cerebroside are present. Furthermore, there are indications that the cerebrosides may comprise a significant fraction of the blood lipids in certain pathological conditions.Method. Procedure for hydrolysis: The procedure of Kirk2 was modified to facilitate hydrolysis of the cerebrosides and filtration of the hydrolysate. Aliquot samples of the lipid extract and blanks for initial and total reduction values2 are measured into 10 cc glass-stoppered graduated cylinders. The solvents are evaporated carefully in a boiling water bath. To each of the samples for initial r...