抗补体活性多糖

补体系统在宿主免疫中具有重要的作用。近年来,由某些中药中纯化的多糖具有明显的抗补体作用。这些多糖大多数含有阿拉伯糖、半乳糖和半乳糖醛酸,分子量范围6.000到500.000。它们的结构很复杂,多为具聚鼠李半乳糖醛酸结构中心的酸性杂多糖和果胶类多糖。这些多糖的抗补体活性可能和整个大分子的结构有关。一旦发生降解活性就大为下降甚至消失。它们都可以经典的方式激活补体系统。大部分也可以改变的方式激活补体系统。     

Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain

Cathepsin D (CTSD) deficiencies are fatal neurological diseases that in human infants and in sheep are characterized by extreme loss of neurons and myelin. To date, similar morphological evidence for myelin disruption in CTSD knockout mice has not been reported. Here, we show that CTSD deficiency leads to pronounced myelin changes in the murine brain: myelin-related proteolipid protein and myelin basic protein were both markedly reduced at postnatal day 24, and the amount of lipids characteristically high in myelin (e.g. plasmalogen-derived alkenyl chains and glycosphingolipid-derived 20- and 24-carbon acyl chains) were significantly lowered compared with controls. These changes were accompanied by ultrastructural alterations of myelin, including significant thinning of myelin sheaths. Furthermore, in CTSD knockout brains there was a pronounced accumulation of cholesteryl esters and abnormal levels of proteins related to cholesterol transport, with an increased content of apolipoprotein E and a reduced content of ATP-binding cassette transporter A1. These results provide evidence for dysmyelination and altered trafficking of cholesterol in brains of CTSD knockout mice, and warrant further studies on the role of lipid metabolism in the pathogenesis of CTSD deficiencies.     

How much undernourishment is required to retard brain myelin development.

This study employs a large population of developing rats designed to range continuously from above a normal, average weight to severely undernourished. The purpose of the study is to determine if brain myelin development is vulnerable to mild growth retardation from chronic hunger, or if brain myelin development is altered only after a certain tolerable amount of growth retardation is exceeded. The brains were examined at a landmark age, weaning, since myelination is one of the most vulnerable features of brain development and its rate of synthesis is highest at this age. Brain size was logarithmically related to body weight, and brain growth retardation increased as the severity of food deprivation increased. There was an additional reduction in the concentration of brain myelin. In contrast to brain weight, the reduction in myelin concentration was linearly related to body size over the full range from well nourished to undernourished. From a population perspective, these data indicate growth retardation from undernourishment in any amount slows brain growth and additionally lowers the concentration of brain myelin; however, individuals, in both well nourished and undernourished groups, vary widely. Implications and cautions of extrapolation to human populations are discussed.     

Purification and characterization of complement-activating acidic polysaccharides from the fruits of Capsicum annuum

Hot water-soluble crude polysaccharide (HCAP-0) that was obtained from the fruits of Capsicum annuum showed potent anti-complementary activity. The activity was unchanged by pronase digestion, but decreased by periodate oxidation. The HCAP-0 was fractionated by DEAE ion-exchange chromatography to give two major fractions, HCAP-II and III. These two fractions were finally purified by gel filtration to give HCAP-IIa, HCAPIIIa1, and IIIa2 fractions that had high anti-complementary activities. The HCAP-IIIa1 and IIIa2 consisted of homogeneous polysaccharides. The anti-complementary activities were unaffected by treatment with polymyxin B, indicating that the modes of complement activation were not due to preexisting lipopolysaccharide. The molecular weight and sugar content of HCAP-IIIa2 had potent anti-complementary activity. The highest yields were 55 kDa and 75.9%, and the molar ratio of galactose (Ara:Gal, 1.0:4.6) was higher than other sugars. The crossed immuno-electrophoresis showed that both classical and alternative pathways were activated by HCAP-IIIa2.     

Activation of the alternative pathway of complement by human peripheral nerve myelin

Destruction of peripheral nerve myelin (PNM) occurs as a consequence of a variety of pathologic conditions affecting the peripheral nervous system. In certain primary demyelinating neuropathies, several lines of evidence implicate complement in the pathogenesis of demyelination. In this study we demonstrate that human PNM consumes complement in vitro in the absence of specific antibody or C1 activation. Furthermore, activation of complement by PNM via the alternative pathway was shown by cleavage of C3 in normal human serum (NHS) and of B in C2-deficient serum (C2d-HS). Increasing consumption of hemolytic activity of C3 in Mg-EGTA-treated NHS was also noted with increasing amounts of PNM. Pronase treatment of PNM abolished C3 consumption, suggesting that a protein component exposed on the surface of myelin participated in the alternative pathway activation. When P0, the major amphiphilic glycoprotein of PNM, was incorporated into artificial lipid bilayers, the Po-liposomes consumed C3 activity in NHS containing Mg-EGTA. Pronase treatment of Po-liposomes abolished C3 consumption to the level of control liposomes, indicating that P0 was responsible for at least part of the activation seen with peripheral myelin.     

Alpha hydroxylation of lignoceric acid to cerebronic acid during brain development. Diminished hydroxylase activity in myelin-deficient mouse mutants.

Alpha Hydroxylation of lignoceric acid (n-tetracosanoic acid) to cerebronic acid (2-hydroxylignoceric acid) by postnuclear preparations of brains from developing rat, mouse, and several neurological mouse mutants was studied. The preparations of brains from jimpy and myelin synthesis deficiency (msd) mice were found to synthesize cerebronic acid at less than 10 percent of their control rates, and those from quaking and dilute-lethal approximately 30 and 50 percent, respectively. The apparent low rate of in vitro hydroxylation by brains of the mutant mice appeared to be due to decreased synthesis rather than increased oxidation of cerebronic acid. Mixing experiments eliminated the possibility of an inhibitor in the mutant or an activator in normal animals. The preparations of brains from wabbler-lethal, ducky, and weaver mice showed normal activity. The developmental pattern of the hydroxylase activity was examined in quaking, jimpy, and their control mice. In normal brains the hydroxylase activity was low in the immediate postnatal period, increased sharply between 10 and 20 days after birth, and fell to a low level following maturation of the brain. The hydroxylase activity in quaking mice changed similarly during brain development but at a much reduced level. The brains of jimpy mice had barely detectable hydroxylase activity which changed little with age and reached a peak at about 15 days postpartum. The subnormal hydroxylase activity in brains of quaking mice and the near absence in brains of jimpy and msd mice correlate with the observations that myelin deficiency is more severe in jimpy and msd than in quaking. These results suggest a close association of the synthesis of cerebronic acid with the synthesis of the characteristic myelin lipid that is cerebroside (N-acyl sphingosine beta-D-galactoside).     

Proteolipids in the developing brains of normal mice and myelin deficient mutants

Abstract— A developmental study of proteolipids from brains of normal mice and two myelin deficient mutants, jimpy and quaking, was performed. The proteolipids were obtained by diethyl ether precipitation of washed total lipid extracts from whole brains and were analysed on polyacrylamide gels containing sodium dodecyl sulphate. The amount of ether precipitable material extractable from normal brains increased almost six-fold between 12 and 21 days posr partum. This increase was not observed with the mutant mice. Polyacrylamide gel electrophoretic analysis of the proteolipid fraction showed it to be heterogeneous, with eight major protein bands. Two of these proteins increased rapidly in quantity in normal mice between 13 and 21 days. These two proteins were present, in severely reduced quantities in the brains of jimpy and quaking mice at all ages examined. One of these proteolipids was the major species present in proteolipid extracts from the brains of normal mature mice. This protein coelectrophoresed with proteolipid isolated from purified myelin and has been tentatively identified as the myelin proteolipid. The other proteolipid which was deficient in jimpy and quaking brains was not characterized, but it appeared to be of extra-myelin origin, and suggests that parts of the brain other than the myelin sheath may be involved in the jimpy and quaking disorders.     

Myelin Galactolipid Synthesis in Different Strains of Mice

Previous studies have indicated that the brains of DBA/2J (D2) mice have a more heavily myelinated CNS than those of C57BL/6J (B6) at postnatal days 17-21. However, the amount of myelin in the brains of F1 (B6 X D2) hybrids is even higher than in their parental strains. To investigate further factors involved in regulating myelinogenesis in these mice, we have focused on the synthesis of cerebrosides and sulfatides, galactolipids enriched in myelin. Brain slices from 14-, 17-, and 21-day-old D2, B6, and F1 mice were incubated with [3H]galactose and [35S]sulfate. After incubation, microsomes, myelin, and oligodendroglial cells were isolated, and the galactolipids were analyzed. At 21 days of age, the labeling of cerebrosides in F1 mice was higher than in D2 and B6 mice when the results were expressed as microsomal or myelin radioactivity per gram wet weight. At 14 and 17 days of age, the labeling of cerebrosides in F1 animals was similar to that in D2 mice and was considerably higher than that in B6 mice. The labeling of sulfatides in F1 animals was significantly higher than in the B6 parent at all ages studied, whereas it remained higher than that in the D2 parent only at 17 days of age. A similar relationship among the strains was observed when the synthesis of myelin galactolipids was estimated by measuring the in vitro activity of UDP-galactose:ceramide galactosyltransferase and 3'-phosphoadenylyl sulfate:galactosylceramide 3'-sulfotransferase. The results indicate that the increased accumulation of myelin galactolipids previously reported in the F1 mice is partially due to enhanced synthetic activity.     

Soluble P-selectin moderates complement-dependent reperfusion injury of ischemic skeletal muscle

P-selectin is an adhesion molecule expressed on activated endothelial and platelet surfaces. The function of the short consensus repeats (SCRs) of P-selectin, homologous with the SCRs of complement regulatory proteins is largely unknown. In a model of murine hindlimb ischemia where local reperfusion injury is partly mediated by IgM natural antibody and classical complement pathway activation, we hypothesized that human soluble P-selectin (sP-sel) would moderate the complement component of the inflammatory response. Infusion of sP-sel supernatant or purified (p) sP-sel prepared from activated human platelets, reduced ischemic muscle vascular permeability by 48% and 43%, respectively, following reperfusion. Hindlimb immunohistochemistry demonstrated negligible C3 staining colocalized with IgM in these groups compared with intense staining in the untreated injured mice. In vitro studies of mouse serum complement hemolytic activity showed that psP-sel inhibited the classical but not alternative complement pathway. Flow cytometry demonstrated that psP-sel inhibited C1q adherence to sensitized red blood cells. From these data we conclude that sP-sel moderates skeletal muscle reperfusion injury by inhibition of the classical complement pathway.     

Production of an anti-complement exo-polymer produced by Auricularia auricula-judae in submerged culture

Exo-polymer (EP) was produced at 1.2 g l(-1) in submerged culture of Auricular auricula-judae. Crude EP (AJ-0) has 70% anti-complementary activity (inhibition of total complementary hemolysis 50%; ITCH50). The activating pathway of the complement system occurred through both the classical and alternative pathways, though the major pathway was the classical one. Fractionation of AJ-0 using Sepharose CL-6B gel chromatography gave three major fractions (AJ-Fr-I, II and III) of which the first was the most active. The mycelial growth and EP production of A. auricula-judae were optimal at pH 6, 25 degrees C and pH 5, 25 degrees C, respectively.     

Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathways of complement

The influence of the state of aggregation of lipopolysaccharides upon their ability to interact with serum complement via either the classical or alternative pathway was studied. The anticomplement properties of two chromatographically distinct fractions of a phenol-extracted lipopolysaccharide isolated from Serratia marcescens were assessed by means of the standard sheep erythrocyte hemolytic assay and an alternative pathway-selective kinetic assay using rabbit erythrocytes. Both the high molecular weight PI fraction and the lower molecular weight PII fraction exerted anti-complement activity as determined in the sheep erythrocyte assay. Conversion of fractions PI and PII to their more soluble triethylamine salt forms resulted in a decrease in sedimentation coefficients and a corresponding loss of anticomplement activity. Further, the anticomplement activity of fractions PI and PII in the sheep erythrocyte assay was inhibited by polymyxin B, indicating a role for the lipid A region. Unlike the PII fraction, only the PI fraction can activate serum complement via the alternative pathway. This activity is not inhibited by polymyxin B, indicating that the response is not lipid A-mediated. Significantly, solubilization of the PI fraction with triethylamine had no effect on its ability to activate the alternative pathway. These studies clearly demonstrate that the interaction between lipopolysaccharides and serum complement is influenced by the state of lipopolysaccharide aggregation. However, this appears to be the case for lipopolysaccharide activation of the classical pathway but not of the alternative pathway.     

Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disease resulting in progressive cognitive decline. Amyloid plaque deposits consisting specifically of β-amyloid peptides that have formed fibrils displaying β-pleated sheet conformation are associated with activated microglia and astrocytes, are colocalized with C1q and other complement activation products, and appear at the time of cognitive decline in AD. Amyloid precursor protein (APP) transgenic mouse models of AD that lack the ability to activate the classical complement pathway display less neuropathology than do the APPQ+/+ mice, consistent with the hypothesis that complement activation and the resultant inflammation may play a role in the pathogenesis of AD. Further investigation of the presence of complement proteins C3 and C4 in the brain of these mice demonstrate that both C3 and C4 deposition increase with age in APPQ+/+ transgenic mice, as expected with the age-dependent increase in fibrillar β-amyloid deposition. In addition, while C4 is predominantly localized on the plaques and/or associated with oligodendrocytes in APPQ+/+ mice, little C4 is detected in APPQ−/− brains consistent with a lack of classical complement pathway activation because of the absence of C1q in these mice. In contrast, plaque and cell associated C3 immunoreactivity is seen in both animal models and, surprisingly, is higher in APPQ−/− than in APPQ+/+ mice, providing evidence for alternative pathway activation. The unexpected increase in C3 levels in the APPQ−/− mice coincident with decreased neuropathology provides support for the hypothesis that complement can mediate protective events as well as detrimental events in this disease. Finally, induced expression of C3 in a subset of astrocytes suggests the existence of differential activation states of these cells.     

Analysis of C4 and the C4 binding protein in the MRL/lpr mouse

Systemic lupus erythematosus is a complement-mediated autoimmune disease. While genetic deficiencies of classical pathway components lead to an increased risk of developing systemic lupus erythematosus, end organ damage is associated with complement activation and immune complex deposition. The role of classical pathway regulators in systemic lupus erythematosus is unknown. C4 binding protein (C4bp) is a major negative regulator of the classical pathway. In order to study the role of C4bp deficiency in an established murine model of lupus nephritis, mice with a targeted deletion in the gene encoding C4bp were backcrossed into the MRL/lpr genetic background. Compared with control MRL/lpr mice, C4bp knockout MLR/lpr mice had similar mortality and similar degrees of lymphoproliferation. There were no differences in the extent of proteinuria or renal inflammation. Staining for complement proteins and immunoglobulins in the kidneys of diseased mice revealed no significant strain differences. Moreover, there was no difference in autoantibody production or in levels of circulating immune complexes. In comparison with C57BL/6 mice, MRL/lpr mice had depressed C4 levels as early as 3 weeks of age. The absence of C4bp did not impact serum C4 levels or alter classical pathway hemolytic activity. Given that immune complex renal injury in the MRL/lpr mouse is independent of Fc receptors as well as the major negative regulator of the classical pathway, new mechanisms for immune-complex-mediated renal injury need to be considered.     

Myelination in rat brain: changes in myelin composition during brain maturation

Abstract— Myelin was isolated from rat brains during development by a procedure giving fractions of constant purity at all ages. The lipid composition of these fractions and of whole brains of littermates was determined. The amount of myelin recovered per brain was a nearly linear function of the logarithm of age from the youngest (15 days) to the oldest (425 days) animals studied. With the exception of the earliest age point, the isolated myelin accounted for approximately 40 per cent of total brain galactolipid, evidence that a constant fraction (calculated to be 60 per cent) of myelin was recovered at all ages. Although the lipid-protein ratio of the myelin was constant with age, marked changes were seen in the amounts of cerebroside, sulphatide, phosphatidylcholine and desmosterol. The total galactolipid increased from 21 per cent of the total lipid at age 15 days to about 31 per cent at maturity. Phosphatidylcholine decreased from 17 to 11 per cent during the same period. Desmosterol decreased from 2.5 per cent of the total sterol to 0.2-0.3 per cent. All of these changes were complete between 2 and 5 months of age; no other ‘lower phase’ lipids showed significant changes with age. Although qualitatively similar to those reported by others, the changes differed in magnitude, with more stability in the levels of cholesterol and phosphatidalethanolamine with development. A sensitive indicator of the maturation of myelin was the mole ratio galactolipid/phosphatidylcholine, which varied from 1.2 at age 15 days to 2.8 at maturity. The maximum rate of myelination occurred at 20 days of postnatal age when myelin was deposited at the rate of 3.5 mg day^?1 brain^?1. However, at this age the rat brain had only 15 per cent of its eventual complement of myelin. The rate of accumulation of cerebroside in the whole brain paralleled that of myelin, and was the only lipid to show this relationship. Myelin deposition appeared to be almost solely responsible for the continued increase in brain weight after about 100 days of age.     

Structure and anti-complementary activity of pectic polysaccharides isolated from the root of Angelica acutiloba Kitagawa

Four pectic polysaccharides (AR-2IIa-IId) with anti-complementary activity have been isolated from a hot-water extract of the root of Angelica acutiloba Kitagawa. Each of these polysaccharides contained a large proportion of GalA together with neutral sugars consisting mainly of Rha, Ara, and Gal. Digestion with endo-alpha-(1----4)-polygalacturonase indicated that AR-2IIa-IIc each contained a large proportion of enzyme-sensitive polygalacturonan regions, and that AR-2IId contained a large proportion of enzyme-resistant regions. When AR-2IId was de-esterified, it became sensitive to the enzyme. These polysaccharides also contained small proportions of enzyme-resistant regions (PG-1) which were rich in neutral sugars. Methylation analysis and base-catalysed beta-elimination studies suggested that each PG-1 contained a rhamnogalacturonan moiety in which 2,4-disubstituted Rha was attached to 4-substituted GalA through position 2 of Rha. Carboxyl-reduction and methyl- and de-esterification of these polysaccharides modulated their anti-complementary activities. Digestion with endo-alpha-(1----4)-polygalacturonase decreased the activities of AR-2IIa and -2IIb, but not those of AR-2IIc and -2IId. Although PG-1 fractions from AR-2IIa-IIc were more active than the original polysaccharides, oligogalacturonide fragments obtained by enzymic digestion had weak or negligible activity. AR-2IIa-IIc expressed their anti-complementary activities mainly via the classical pathway, but AR-2IId and each PG-1 expressed their activities via both the classical and alternative pathways.     

Identification with a Monoclonal Antibody of a Phylogenetically Conserved Brain-Specific Determinant on a 130,000 Molecular Weight Glycoprotein of Human Brain

Human brain glycoproteins depleted of Thy-1 antigen were used to immunise Balb/c mice for monoclonal antibody production. The F3-87-8 antibody described in this paper interacts with a determinant present in large amounts on all human brain subregions studied (cerebral cortical grey matter, white matter, caudate, thalamus, dentate nucleus, putamen, cerebellar cortex) but absent from all other tissues examined (liver, heart, kidney, spleen, thymus, lymph node, erythrocyte, adrenal gland, and peripheral nerve). The determinant is conserved in mammalian evolution, as the brains of the rat and dog have amounts equal to that found in human brain. Balb/c mouse brain has approximately one-third as much antigen activity as these other mammalian brains, whereas brains of the frog and chicken have no detectable antigenic activity. Developmental studies showed that 16-week human foetal brain and neonatal dog brain had little or no antigen activity, indicating a dramatic increase in the amount of the determinant with brain maturation. Biochemical studies showed that the F3-87-8-bearing molecule was a major sialoglycoprotein of human brain with an apparent molecular weight of 130,000. It was shown by immunofluorescence to be particularly localised in what appeared to be fibre tracts in the thalamus and basal ganglia, and in the dentate nucleus, although all regions including grey matter were stained.     

A Pi Form of Glutathione-S-Transferase Is a Myelin-and Oligodendrocyte-Associated Enzyme in Mouse Brain

The pi form of glutathione-S-transferase (GST), previously found to be oligodendrocyte associated, has also been found in myelin. In the brains of adult mice, immunocytochemical staining for a pi form of GST was observed in myelinated fibers, as well as oligodendrocytes. In contrast, and as previously found in rats, positive immunostaining for mu forms occurred in astrocytes and not in oligodendrocytes or myelinated fibers. Double immunofluorescence staining strengthened the conclusion that pi was in oligodendrocytes and myelin in mouse brains. The results of enzyme assays performed on brain homogenates and purified myelin indicated that GST specific activities in mouse brain myelin were almost as high (0.8-fold) as those in mouse brain homogenates. Low, but reproducible, GST activities were also observed in myelin purified from rat brains, in which pi had been demonstrated in oligodendrocytes and mu in astrocytes. The pi form was also stained by the immunoblot technique in myelin purified from mouse brain. It was concluded that pi is a myelin associated, as well as oligodendrocyte associated, enzyme in mouse brain, and possibly also in rat brain. This is the first report of localization of GSTs in mouse brain and of GST in myelin.     

Changes in Brain Tissue and Behavior Patterns Induced by Single Short-Term Fasting in Mice

In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.     

Up-Regulation of Carbonic Anhydrase Isozyme IV in CNS Myelin of Mice Genetically Deficient in Carbonic Anhydrase II

Abstract: Carbonic anhydrase (CA) II is the major CA isozyme in the brain, where it participates in acid-base homeostasis, fluid transport, and myelin synthesis. The CA II deficiency [CA(II)D] mutation in the mouse results in structural changes in the glial cells in the CNS and in decreased susceptibility to seizures, but no detectable changes in myelin yield and ultrastructure. We compared the CA isozymes in brain and spinal cord fractions, as well as in purified myelin, between CA(II)D and control mice. CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in soluble and membrane-associated fractions and pure myelin. Western blots of purified myelin showed a band corresponding to CA IV in CA(II)D mice. This band was weak or undetectable in myelin samples from normal mice. Immunocytochemical staining demonstrated CA IV in oligodendrocytes and myelinated tracts in normal mouse brains and stronger staining of the same structures in brains of CA(II)D mutants. We conclude that CA(II)D mutation in the mouse up-regulates CNS CA IV. We speculate that this up-regulation could mitigate the effect of CA(II)D on myelin formation and maintenance.     

THE FATTY ACID COMPOSITION OF PHOSPHOLIPIDS AND GLYCOLIPIDS IN JIMPY MOUSE BRAIN

Abstract— Phospholipids and sphingolipids from brains of normal and Jimpy mice were isolated in a pure form by thin-layer chromatographic procedures. The fatty acid composition of the major phospholipids, i.e. ethanolamine glycerophospholipids, serine glycerophospholipids, choline glycerophospholipids and inositol glycerophospholipids, as well as sphingomyelin, cerebrosides and sulphatides was determined by gas-liquid chromatography. A specific fatty acid pattern for each of the four glycerophospholipids was found. The fatty acid composition of inositol glycerophospholipid, which has not previously been studied in mouse brain, was characterized by a high concentration of arachidonic acid. After 16 days of age, fatty acid analysis showed definite differences between the phospholipids from normal and mutant brains. A small increase of polyunsaturated fatty acids in glycerophospholipids of ethanolamine, serine and choline from the Jimpy central nervous system was found, which has been explained by the myelin deficiency. Sphingomyelin, cerebrosides and sulphatide analyses showed a wide distribution of saturated and mono-unsaturated fatty acids in both normal and mutant mice. A reduction in the amount of long-chain fatty acids was demonstrated in mutant brain sphingolipids; in sulphatides and cerebrosides, the amount of non-hydroxy fatty acids was reduced to a greater extent than in sphingomyelin. The distribution of fatty acids in sphingolipids from the myelin and microsomal fractions was also investigated in both types of mice. Cerebrosides were characterized by a high content of long-chain fatty acids in myelin as well as in microsomes. Sulphatides and sphingomyelin, on the other hand, showed a higher content of medium-chain fatty acids in microsomes than in myelin. In the mutant brain, the amount of long-chain fatty acids was reduced in both subcellular fractions. The deviation from normal in the pattern of fatty acid distribution in Jimpy brain is discussed in relation to the current concepts of glycolipid biosynthesis.