Normal Adult Human Brain Research Articles

Regional distribution of bombesin and seven other regulatory peptides in the human brain

In order to compare within the same brains the quantitative distributions of a range of neuropeptides, bombesin, N- and C-terminal glucagon, cholecystokinin, neurotensin, somatostatin, substance P and vasoactive intestinal polypeptide immunoreactivities were determined by radioimmunoassay in 24 regions of 5 normal adult human brains. Each peptide showed a different distribution pattern. Of the peptides not previously mapped in detail in the human brain, bombesin-like immunoreactivity was present in all regions with the highest concentrations in particular areas of the hypothalamus, septal nuclei, nucleus accumbens, globus pallidus, amygdala, periaqueductal grey and substantia nigra. C- and N-terminal glucagon immunoreactivities were detected only in the ventromedial hypothalamus. The concentrations of the remaining 5 peptide immunoreactivities, and their molecular forms, were in good general agreement with those reported individually by others in both human brains and those of experimental animals. The quantitative mapping of the regulatory peptides in the human brain provides an essential base for further comparative study in diseased postmortem brains.

Isolation and characterization of a novel trisialoganglioside, GT1a, from human brain.

A novel trisialoganglioside has been isolated from normal adult human brain in a yield of 0.6% of the total gangkioside. By graded neuraminidase treatment, mild acid hydrolysis and periodate oxidation analysis, the ganglioside was identified as GT1a having the following structure: NeuAc(alpha, 2-8)NeuAc(alpha, 2-3)Gal(beta, 1-3)GalNAc(beta, 1-4) [NeuAc(alpha, 2-3)]Gal(beta, 1-4)Glc(1-1)ceramide.

Steryl esters and their relationship to normal and diseased human central nervous system

The composition and distribution of steryl esters in human diseased or developing brain tissue has been studied. The abnormal brain conditions included sudanophilic leukodystrophy, multiple sclerosis plaque, subacute sclerosing panencephalitis, and an old cerebral infarction and two types of brain-derived tumors. In addition to the above abnormal tissue, steryl esters were also examined in developing and normal adult human brain. It was found upon subcellular fractionation that the steryl ester was localized mainly in the soluble nonparticulate material. A cholesteryl ester-rich fraction, floating on top of distilled water after centrifugation, was recovered only in the developing brain or in instances where there was myelin damage. The sterol portion of the steryl ester was largely cholesterol. The fatty acid moiety was mainly composed of C(16), C(18), and C(20) fatty acids. The dominant fatty acid was oleic acid, and the proportion of this fatty acid increased in demyelination. Although there were great differences in the quantities of steryl ester found, the fatty acid profiles of normal developing and adult brain were quite similar. As has been noted by others, the fatty acid composition of brain steryl esters most closely resembles that of brain phosphatidylcholine.

The nature of sulphation of uronic acid-containing glycosaminoglycans catalysed by brain sulphotransferase.

Abstract—A sulphotransferase system of rat brain catalyses the transfer of sulphate from 3′‐phosphoadenosine 5′‐phosphosulphate to the low‐sulphated glycosaminoglycans isolated from normal adult human brain. These were shown to be precursors of higher‐sulphated glycosaminoglycans by DEAE‐Sephadex column chromatography and paper electrophoresis. Nitrous acid degradation and mild acid hydrolysis of enzymically‐sulphated fractions further confirmed the presence of heparan sulphate in human brain.A partially purified sulphotransferase preparation was obtained from neonatal human brain using chondroitin‐4‐sulphate as sulphate acceptor. This sulphotransferase catalyses the transfer of sulphate to the various uronic acid containing glycosaminoglycans. Heparan sulphate was the best sulphate acceptor followed by dermatan sulphate, N‐desulphoheparin, chondroitin‐4‐sulphate and chondroitin‐6‐sulphate in decreasing order. Sulphotransferase obtained from 1‐day‐old rat, rabbit and guinea pig brain also had the same pattern of specificity towards various sulphate acceptors.This sulphotransferase catalyses both N‐sulphation and O‐sulphation. Studies on the sulphotransferase obtained from both rat and human brain of various age groups indicate that the ratio of N‐sulphation: O‐sulphation decreases as the brain matures.

Regulation of proliferation and movement of human glialike cells in culture

The control of DNA synthesis and locomotion have been investigated in vitro in serially propagated astrocyte-like lines from normal adult human brain. DNA synthesis was measured autoradiographically as the percentage of cells showing uptake of tritiated thymidine during a 24 h period. In the period after subcultivation when the cell number increased rapidly, about 40–80% of the cells participated in DNA synthesis. After 10–15 days when the number of cells had stabilized at a level of about 60,000/cm 2, the percentage of labeled cells dropped to 1% or less, indicating strict control of DNA synthesis in a complete monolayer. Addition of fresh medium caused a slight temporary increase of DNA synthesis in stationary layers. Analysis of the length of the cell cycle periods gave the following values: T, 22 h, G1, 8.5 h, S, 8 h, G2, 4.5 h, M, 1 h. There was no evidence for division by amitosis. Cell locomotion was analysed by time-lapse cinematography. Glia cells were mobile in a sparse culture, but had a tendency to form adhesions along areas of mutual contact. These were not always sufficiently strong to prevent cytoplasmic and even nuclear overlapping. When a complete monolayer had formed, the cells were essentially immobile and no ruffled membranes were seen. The results indicate that adult human glia cells have unusually well developed growth control mechanisms in vitro and should lend themselves well to the experimental study of such controls.

Quantification and fatty acid and fatty aldehyde composition of ethanolamine, choline, and serine glycerophosphatides in human cerebral grey and white matter

The quantities of ethanolamine glycerophosphatides (EGP), choline glycerophosphatides (CGP), and serine glycerophosphatides (SGP) were determined in the grey and white matter from three apparently normal adult human brains. In each locale the quantities decreased from EGP through CGP to SGP. The quantities of aldehydes in these lipids were also determined. In grey matter the aldehyde content (expressed as per cent of fatty acids plus aldehydes) of EGP, CGP, and SGP was 22, 0.3, and 0.2% respectively; while in white matter the proportions were 49, 0.8, and 13%, respectively. Palmitaldehyde, stearaldehyde, and olealdehyde made up 90% of the aldehydes found. White matter glycerophosphatides contained much more olealdehyde than those from grey matter. EGP and SGP contained much larger proportions of C20 and C22 polyenoic acids from grey matter than from white matter. CGP, on the other hand, had a similar fatty acid composition, comprised mainly of 16:0, 18:0, and 18:1 acids, in each locale. The differences in fatty acid composition of these three glycerophosphatides may be related to the higher myelin content of white matter.

Incorporation of Acetate-1-C<sup>14</sup> Into Cholesterol by Human Intracranial Tumors <italic>In Vitro</italic><xref ref-type="fn" rid="FN1">2</xref>

Normal adult human brain does not incorporate C14-labeled acetate into cholesterol in vitro. Under similar conditions, glioblastoma multiforme, astrocytomas, meningiomas, neurofibromas, acoustic neurinomas, and ependymomas can accomplish this conversion. The synthetic pathway in the tumors appears to be similar to that in normal liver tissue. Cholesterol biosynthesis in human central nervous system tumors is inhibited by oral administration of vanadium as diammonium oxytartratovanadate.

Normal oligodendrocytes in tissue culture: A preliminary report on the pulsatile glial cells in tissue cultures from the corpus callosum of the normal adult rat brain

1. 1. Cells believed to be oligodendrocytes have been obtained in outgrowths from explants in vitro of normal adult rat corpus callosum. These cells show a characteristic rhythmic pulsatility apparently identical with that described in 1935 by Canti, Bland and Russell in the case of oligodendrocytes obtained in culture from oligodendroglioma of the human brain. We believe also that we have seen similar cells in a few tissue culture preparations from the cortex cerebri of the normal adult human brain. 2. 2. The morphology of this cell in the living state in culture has been described and some analysis has been attempted of its pulsation as studied by timelapse ciné-photomicrography. 3. 3. Some possible physiological and pathological implications of this pulsatile activity of oligodendrocytes are discussed.