Origins of the Human Brain

Origins of the Human Brain. J. P. Changeux and J. Chavaillon. eds. Oxford, England: Oxford University Press, 1995. 321 pp.     

Nitrogen Metabolism of the Human Brain

Cerebral nitrogen metabolism was studied in 29 healthy nonobese volunteers by means of a catheterization technique. Arterial levels and arterial-jugular venous (A-JV) concentration differences for amino acids, urea, ammonia, 5-oxoproline, glucose, and oxygen were measured in the basal, postabsorptive state and during an intravenous infusion of a commercial amino acid solution. In the basal state positive A-JV differences, indicating a net brain uptake, were noted for 12 of 22 amino acids as well as for ammonia. There was no significant net exchange for urea or for 5-oxoproline. During amino acid infusion, resulting in a 150-300% rise in arterial amino acid levels, the brain uptake of isoleucine, leucine, and tyrosine increased significantly, and a similar tendency was seen for most other amino acids. The infusion was accompanied by a 100% rise in arterial ammonia levels and a 10% increase in urea concentration. For ammonia the small positive A-JV difference in the basal state became markedly greater during amino acid infusion, whereas no significant alteration was noted for urea exchange across the brain. The A-JV differences for glucose and oxygen were positive in the basal state and unchanged during the infusion. The present findings demonstrate that in the basal state (a) there is a significant net brain uptake of most amino acids; (b) no single amino acid, urea, or 5-oxoproline is released from the brain; and (c) ammonia uptake occurs both in this state and during an amino acid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of Cholecystokinin from the Human Brain

Human forms of cholecystokinin have not previously been characterized chemically. In this study, we have extracted and purified the predominant molecular form of cholecystokinin present in human cerebral cortex. The peptide was characterized by amino acid analysis, automated peptide sequencing, and fast atom bombardment mass spectrometry. It appears to be identical to porcine cholecystokinin-octapeptide, with the sequence of Asp-Tyr(SO3)-Met-Gly-Trp-Met-Asp-Phe(NH2). This structural identity is consistent with the observations that the peptide in human brain and porcine cholecystokinin-octapeptide are recognized similarly by a battery of antisera to porcine cholecystokinin; that they coelute from several chromatographic systems, including gel filtration, ion exchange, and reversed-phase; and that they possess similar biological activities.     

d-Aspartate in Human Brain

The presence of the biologically uncommon D-aspartic acid (D-aspartate) in human brain white matter has been previously reported. The earlier study has now been expanded to include D/L-aspartate ratios from 67 normal brains. The data show that the D-aspartate content increases rapidly from 1 year to approximately 35 years of age, levels off in middle age, and then appears to decrease somewhat. The D-aspartate content in gray matter remains at a consistently low level (half of that found in white matter) throughout the human life span. Within the limitations of current analytical methods, there was no detectable difference in D/L-aspartate ratios in white and gray matter of brains with Alzheimer's disease and several other pathologies when compared with brains of normal subjects. However, the presence of a significant D-aspartate level in white matter during the adult life span may lead to changes in protein configuration related to dysfunctions associated with the aging brain.     

Parvalbumin in Human Brain

Parvalbumin was isolated from human cerebral cortex and biceps and triceps muscles by HPLC. The immunological properties of the human protein and the mobility in two-dimensional polyacrylamide gels were similar to that of parvalbumin isolated from the muscles of rat, mouse, rabbit, and chicken. The tryptic peptide maps of the human parvalbumin, however, differed considerably from all other parvalbumins, indicating a distinct primary structure. The immunolabeled cells in the hippocampus of the human brain were of different sizes and forms; they occurred in all subfields and probably represent interneurons.     

Characterization of Human Brain Phenolsulphotransferase

Abstract: Both human phenolsulphotransferase M (for monoamines) and P (for phenol) were detected in eight out of twelve brains examined postmortem. Activity values were low compared with those in other human tissues and in brains from other species. The activity of both forms was unevenly distributed in different brain regions in a pattern different from that of the mono amines. From a study of substrate specificity, K _m values, and inhibitor sensitivity, the two forms of the human brain enzyme did not appear to differ from their counterparts in platelet.     

Male Microchimerism in the Human Female Brain

In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n = 26), or women who had Alzheimer’s disease (n = 33). We report that 63% of the females (37 of 59) tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p = 0.03) and concentration (p = 0.06) of male microchimerism in the brains of women with Alzheimer’s disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.     

Membrane Lipids in the Aging Human Brain

The membrane lipid composition of human brain has been studied in 21 men and 18 women 60-97 years of age. This brain tissue series is unique, because it has been obtained only from individuals who lived a normal social life in their own homes and died suddenly and unexpectedly from arteriosclerotic heart disease or ruptured aortic aneurysms. They had no history of neurological or psychiatric disease. Macroscopic and microscopic examinations ruled out any signs of organic brain disorder. The percentage of solids diminished continuously during the whole period, but the marked individual differences suggested large variations in the hydration of the brain. The content of membrane lipids also diminished continuously up to 90 years of age, when a marked diminution in level of gangliosides and cerebrosides occurred, a result indicating a rapid reduction in amount of neuronal membranes and myelin. The clinical implications of the variation in brain hydration and the rapid loss of membrane lipids after 90 years of age are discussed.     

Distribution of Cholecystokinin-Like Peptides in the Human Brain

Abstract: The regional distribution of cholecystokinin-like immunoreactivity (CCK-LI) in postmortem human brain material has been investigated. CCK-LI was concentrated particularly in the forebrain (all cerebral cortical areas, amygdala, and hippocampus), with smaller amounts in the basal ganglia, hypothalamus, and periventricular grey. Lowest amounts of CCK-LI were found in the thalamus, cerebellum, and spinal cord.     

Gangliosides in Human Fetal Brain

The ganglioside concentration and composition were determined in 42 human fetal brains from gestational week 10 to 22, a period that is morphologically characterized by rapid neuroblast proliferation and migration. The ganglioside concentration was constant during this period, approximately 1 mumol of ganglioside sialic acid/g of fresh tissue weight. At gestational week 10 the ganglioside pattern was dominated by gangliosides of the ganglio b series, with the major ganglioside being GT1b, contributing 40% of total ganglioside sialic acid, whereas GD1b and GD3 contributed only 15 and 10%, respectively. The proportion of b series ganglioside decreased to gestational week 22, with the most pronounced relative reduction affecting GD3, but also GT1b and GD1b to a lesser extent. The ganglioside GQ1b increased in content from gestational week 10 and peaked around week 16. The proportion of GD1a increased markedly between gestational week 12 and 14 and slowly between week 14 and 18 and then increased rapidly from week 20. Ganglioside GM1 underwent a similar change. Gangliosides of the lacto series contributed 6-10% of ganglioside sialic acid between gestational week 10 and 15, and thereafter the proportion slowly decreased. 3'-isoLM1 decreased rapidly in content from gestational week 10 (20 nmol/g of fresh weight) to week 22 (less than 0.5 nmol/g of fresh weight), whereas the gangliosides of the neolacto series (3'-LM1 and 3',8'-LD1) showed a slower and less marked decline in level. The biological significance of the ganglioside changes is discussed.     

Modeling the Impact of Lesions in the Human Brain

Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous (“resting-state”) neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.