The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain, i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18:1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer's disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18:1, is not significantly altered in Alzheimer's disease, but there is a substantial increase in the relative amounts of the saturated components 14:0, 16:0 and 18:0. This is paralleled by a decrease in the polyunsaturated FA 20:4, 22:4 and 22:6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process.

The neutral and phospholipid compositions of various regions of the human brain were analyzed using autopsy material covering the life period between 33 and 92 years of age. The protein content was also measured and, on a weight basis, this content is unchanged in the cerebellum, pons, and medulla oblongata, whereas in the 90-year-old group it decreases in the hippocampus, gray matter, and nucleus caudatus. In white matter, the protein content decreases continuously with age. The phospholipid composition is characteristic of the region investigated, but remains unchanged during aging. The total phospholipid content exhibits only a 5-10% decrease in the oldest age group. The content of dolichol and its polyisoprenoid pattern are also characteristic of the region analyzed. Between 33 and 92 years of age, the amount of dolichol in all portions of the brain increases three- to fourfold, but the isoprenoid pattern remains constant. The level of dolichyl-P varies between different regions, but only a moderate increase is seen with age. Ubiquinone content is highest in the nucleus caudatus, gray matter, and hippocampus, and in all areas this content is decreased to a great extent in the oldest age groups. All regions of the human brain are rich in cholesterol, but alterations in the amount of this lipid are highly variable during aging, ranging from no change to a 40% decrease.

Serious viral CNS infections during childhood appear to be associated with the later development of schizophrenia and nonaffective psychoses. The association with specific viruses suggests that the risk is related to infectious agents with a propensity to invade the brain parenchyma.

No abstract

The flagellum protein flagellin of Listeria monocytogenes is encoded by the flaA gene. Immediately downstream of flaA, two genes, cheY and cheA, encoding products with homology to chemotaxis proteins of other bacteria, are located. In this study we constructed deletion mutants with mutations in flaA, cheY, and cheA to elucidate their role in the biology of infection with L. monocytogenes. The ⌬cheY, ⌬cheA, and double-mutant ⌬cheYA mutants, but not ⌬flaA mutant, were motile in liquid media. However, the ⌬cheA mutant had impaired swarming and the ⌬cheY and ⌬cheYA mutants were unable to swarm on soft agar plates, suggesting that cheY and cheA genes encode proteins involved in chemotaxis. The ⌬flaA, ⌬cheY, ⌬cheA, and ⌬cheYA mutants (grown at 24°C) showed reduced association with and invasion of Caco-2 cells compared to the wild-type strain. However, spleens from intragastrically infected BALB/c and C57BL/6 mice showed larger and similar numbers of the ⌬flaA and ⌬cheYA mutants, respectively, compared to the wild-type controls. Such a discrepancy could be explained by the fact that tumor necrosis factor receptor p55 deficient mice showed dramatically exacerbated susceptibility to the wild-type but unchanged or only slightly increased levels of the ⌬flaA or ⌬cheYA mutant. In summary, we show that listerial flaA, cheY, and cheA gene products facilitate the initial contact with epithelial cells and contribute to effective invasion but that flaA could also be involved in the triggering of immune responses.

SUMMARYAttachment and neuritic transport of herpes simplex virus (HSV) type 1 (McIntyre) were studied in a cell culture system with dissociated cells of rat dorsal root ganglia. The two-chamber cell culture system containing a diffusion barrier penetrated by neurites of cultured sensory neurons permitted infection of neurites extending outside the diffusion barrier without exposure of the neuronal cell soma. HSV adsorbed to neuritic extensions and reached the neuronal soma within 1.5 h post-inoculation. Neuritic uptake and transport of HSV were inhibited in the presence of cytochalasin B. Internalization of virus in neurites was preceded by attachment of virus to the neurite plasma membrane. Neurites transported viral nucleocapsids (NC) through the diffusion barrier of the cultures. Destruction of the neuritic extensions before or shortly after peripheral virus inoculation blocked spread of infection to the cell soma. No infection was established when neuritic extensions were exposed to viral NC and NC were then not observed inside the neurite plasma membrane. Virus produced in neurons, when HSV was inoculated into the inner culture chamber containing the neuronal cell bodies, was transported as enveloped virus in cytoplasmic vesicles from the neuronal cell body towards the periphery. Schwann cells were infected by viropexis. Shortly after infection virions were observed in vacuoles of the cytoplasm.

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The lipid compositions of 10 different brain regions from patients affected by Alzheimer's disease/senile dementia of Alzheimer's type were analyzed. The total phospholipid amount decreased somewhat in nucleus caudatus and in white matter. The cortical areas that are morphologically affected by Alzheimer's disease, i.e., frontal and temporal cortex and the hippocampus, showed elevated contents of lipid solvent-extractable phosphatidylinositol. Sphingomyelin content was decreased in regions rich in myelin. There was a 20-50% decrease in dolichol amount in all investigated parts of the brain, but no change was seen in the polyisoprenoid pattern. Levels of alpha-unsaturated polyprenes were decreased in Alzheimer brains. Dolichyl-phosphate content increased in most regions, up to 100%. In both control and Alzheimer tissue almost all of the dolichyl-phosphate was covalently bound, apparently through glycosylation. Cholesterol amounts were highly variable but mostly unchanged, whereas ubiquinone concentrations increased by 30-100% in most regions in brains affected by Alzheimer's disease. These results demonstrate that both phospholipids and neutral lipids are modified in brains affected by Alzheimer's disease/senile dementia of Alzheimer's type.