Gene expression in the hippocampus of behaviorally stimulated rats: analysis by DNA microarray.

Gene expression in the hippocampus of rats exposed to a brief vigorous swimming task was analyzed by DNA microarray hybridization against 5184 known DNA sequences. Each of 12 rats consistently expressed 17% of the genes probed on the microarrays. Transcripts from genes for energy metabolism, development and differentiation, and gene regulation were expressed in the hippocampus to the highest degree relative to their availability on the microarray. The number of genes that were differentially expressed in behaviorally stimulated compared to undisturbed rats was estimated at 2.7% of all expressed genes. Behavioral effects were relatively greater on expression of genes for control of the cell cycle and apoptosis, development and differentiation, protein processing and gene regulation. The magnitude of differential expression due to behavioral stimulation was lower than that generally reported for developmental processes and disease states. Thus the impact of acute behavioral stimulation on steady-state levels of gene expression was small, but (with four replicates per condition) detectable at a statistically significant level. The effects of behavioral stimulation on transcription may thus involve changes in the expression of a relatively small number of genes to a low but reproducible degree.

Development changes and regional variation in the ganglioside composition of the rat hippocampus.

Individual gangliosides were extracted and quantified from intact and subregionally dissected hippocampal formations during the first 3 weeks of postnatal development in the rat. The 4 major gangliosides were all found to be rapidly increasing relative to brain weight prior to the onset of significant synaptogenesis, but quantitative changes in the final proportion of each ganglioside resulted from different rates of accumulation of gangliosides D1a, D1b, and T1b, beginning about the time of synaptic maturation and dendritic arborization but prior to the onset of myelination and neurophysiological activity. A ganglioside pattern difference characterized by lower levels of T1b and D1b in the area dentata of middle and dorsal aspects of the hippocampal formation coincides with developmental gradients previously observed by morphogenetic criteria for these subregions. These ganglioside differences may thus be developmentally regulated, but the persistence into adulthood of higher levels of D1a in the dentate area suggests that some ganglioside pattern differences may be intrinsic to the unique neuronal cell populations present in different areas of the hippocampus.

Peptides from pigeon cerebrum: two-dimensional fingerprinting and amino acid analysis.

The number and heterogeneity of endogenous peptides from pigeon cerebrum were studied by two-dimensional peptide fingerprinting. A highly consistent pattern of 8-9 peptides in the 1000-5000 molecular weight range was obtained from each cerebral sample. Amino acid analysis of the peptide material indicated that 30% of the identified residues were dicarboxylic amino acids and 30% were alphatic amino acids. There was no evidence for the presence of arginine or half-cystine in the peptide fraction.

Glucosamine incorporation into rat cerebrum: effect of adrenalectomy, corticosterone, exercise, and training.

Incorporation of D-[I-14C]glucosamine into various metabolic fractions was studied in an experiment designed to quantify the relative influence of physiological and behavioral factors. Different physiological states were established by sham operation (S), adrenalectomy (A), and adrenalectomy plus corticosterone replacement (H). Within each physiological condition the behavioral state was varied by swim-escape training (E), swimming exercise (X) or nonswimming controls (C). Adrenalectomy caused a generalized increase in label uptake by cerebral cortex and hippocampus, but precursor levels in the blood were elevated also, suggesting a systemic physiological effect. Behavioral state had no effect on overall uptake, but did influence the distribution of label between soluble and membrane-bound glycoproteins. These results indicate that D-[I-14C]glucosamine is an effective glycoprotein and ganglioside precursor in behavioral experiments, provided corrections for the influence of systemic physiological factors are made.

Circadian-dependent effect of melatonin on dopaminergic D2 antagonist-induced hypokinesia and agonist-induced stereotypies in rats.

Although a melatonin/dopamine relationship has been well established in nonmotor systems wherein dopamine and melatonin share an antagonist relationship, less clear is the role melatonin may play in extrapyramidal dopaminergic function. Therefore, the purpose of the present experiments was to examine the relationship between melatonin and the dopaminergic D2 receptor system and behavior. Hypokinesia was induced in male Sprague-Dawley rats with fluphenazine (D2 antagonist, 0.4 mg/kg ip) and stereotypies with apomorphine (D2 agonist, 0.6 mg/kg sc) during the light (1200 h) and dark (2200 h) phases. As expected, fluphenazine induced severe hypokinesia during the light phase (482 +/- 176 s); however, unexpectedly, fluphenazine-induced hypokinesia during the dark was almost nonexistent (25 +/- 6 s). Furthermore, melatonin treatment (30 mg/kg ip) produced a strong interaction with fluphenazine in that it reduced fluphenazine-induced hypokinesia by nearly 80% in the light (112 +/- 45 s) but paradoxically increased the minimal fluphenazine-induced hypokinesia in the dark by more than 60% (70 +/- 17 s). Melatonin also reduced apomorphine-induced stereotypies by nearly 40% in the light but had no effect in the dark. Taken together, these data show (1) a strong and unexpected nocturnal effect of fluphenazine on hypokinesia and (2) provide support for an antagonistic melatonin/dopaminergic interaction in the context of motor behavior and D2 receptor function which appears to be critically dependent on the light/dark status of the dopaminergic system.

Assessing the plausibility of life on other worlds.

As the field of astrobiology matures and search strategies for life on other worlds are developed, the need to analyze in a systematic way the plausibility for life on other planetary systems becomes increasingly apparent. We propose the adoption of a simple plausibility of life (POL) rating system based on specific criteria. Category I applies to any body shown to have conditions essentially equivalent to those on Earth. Category II applies to bodies for which there is evidence of liquid water and sources of energy and where organic compounds have been detected or can reasonably be inferred (Mars, Europa). Category III applies to worlds where conditions are physically extreme but possibly capable of supporting exotic forms of life unknown on Earth (Titan, Triton). Category IV applies to bodies that could have seen the origin of life prior to the development of conditions so harsh as to make its perseverance at present unlikely but conceivable in isolated habitats (Venus, Io). Category V would be reserved for sites where conditions are so unfavorable for life by any reasonable definition that its origin or persistence there cannot be rated a realistic probability (the Sun, gas giant planets). The proposed system is intended to be generic. It assumes that life is based on polymeric chemistry occurring in a liquid medium with uptake and degradation of energy from the environment. Without any additional specific assumptions about the nature of life, the POL system is universally applicable.

Phylogeny and ontogeny of vertebrate brain gangliosides.

Gangliosides evolved relatively recently in the history of life, thus their contribution to fundamental cellular processes must be ancillary to or superimposed on preexisting mechanisms. Brain ganglioside patterns vary along taxonomic lines in a fairly conservative fashion, indicating that general ecophysiological factors have probably provided the major selective constraints. During brain development in birds and mammals, gangliosides pass through a transient stage of pattern complexity that may reflect their reptilian ancestry. While this ganglioside heterogeneity could provide positional information within the developing tissue, it might merely reflect a necessary but incidental transition to the handful of major gangliosides essential to mature brain function.

Acrobat to academic: a sketch of the life and career of Frederick E. Samson, Jr.

Fred Samson's career began in osteopathy and show business. After service as a medic during World War II, he earned a doctoral degree in physiology at the University of Chicago and joined the faculty of the University of Kansas in Lawrence in 1952. There he conducted pioneering research on cerebral energy metabolism and axoplasmic transport while inspiring a generation of students in the classroom and lab. During the mid 1960s, he began a fruitful and lasting collaboration with the Neurosciences Research Program and its founder, Francis O. Schmitt. In 1973 he became director of the Ralph Smith Mental Retardation Research Center in Kansas City, where he added metabolic mapping of the brain in relation to seizure activity and drug toxicity to his research accomplishments. He retired in 1989, still pursuing new problems and continuing to inspire colleagues with his enthusiasm for neurochemistry and the joy of science.

Phylogenetic and regional variations in brain gangliosides of tetrapods.

1. Ganglioside patterns were analyzed from four neural tissues (medulla, midbrain, forebrain and retina) in a representative from each of the four tetrapod classes. 2. Regional variations in ganglioside patterns were noted within some species, but differences were greater across phylogenetic lines. 3. These results suggest that evolutionary history plays a greater role than neural differentiation in the expression of brain ganglioside patterns.

Amphibian brain gangliosides: pattern analysis by two-dimensional thin-layer chromatography.

Gangliosides were extracted from brains from ten amphibian species, representing six different genera from two orders, and analyzed by two-dimensional thin-layer chromatography (2D-TLC). Qualitatively distinct differences were detected at the family level, while differences within the same family or genus were primarily quantitative.

Glucosylceramide in the androgen-responsive kidney of the lizard Anolis carolinensis.

During the spring breeding season of the American chameleon, Anolis carolinensis, elevated levels of glucosylceramides which contain hydroxy fatty acids are produced in the kidneys of males but not females. Hyperproduction of this glycolipid is also induced by testosterone. The testosterone-induced hypertrophy of epithelial cells in the proximal tubules of the mouse kidney seems an analogous phenomenon and an elevated concentration of specific glycolipids in the male mouse kidney has been previously demonstrated. Thus the formation of renal glycolipids in response to testosterone may be a widespread feature in vertebrates.

Developmental variation in monosialoganglioside content of embryonic chick retina and tectum.

Monosialogangliosides were extracted from the retinas and optic tecta of chick embryos at 6-12 days of incubation, and analyzed by high-performance liquid chromatography. The dominant monosialoganglioside was found to be N-acetylgalactosaminyl (N-acetylneuraminyl) galactosylglucosylceramide (GM2). The specific concentration of GM2 in both the retina and tectum rose to a peak at 8-9 days of incubation, then declined. At day 10, GM2 was significantly lower in the dorsal than in the ventral or temporal quadrants of the retina. The same trend to a lesser degree was seen in the tectum. These results demonstrate striking variations in the monosialoganglioside content of the retina and tectum during formation of the retinotectal projection, and suggest that topological gradients may be a consequence of these developmental and spatial variations.

Ganglioside patterns during cerebral development in the normal and reeler mouse.

Gangliosides were extracted from cerebral tissue of reeler and normal mice, and analyzed by two-dimensional thin-layer chromatography at embryonic and postnatal ages. The ganglioside pattern changed substantially as development proceeded in the telencephalon of both reeler and normal mice, but was the same at any given age for both conditions, despite the marked histological differences between reeler and normal samples. These results indicate that abnormal ganglioside patterns do not result from the reeler mutation at early stages of brain development, and that the cell misalignment characteristic of the reeler phenotype involves molecules other than gangliosides.

Uptake of exogenous gangliosides by rat brain synaptosomes.

Synaptosomes incorporated mixed brain gangliosides at a rapid initial rate followed by a slower phase of net movement from the protein-associated fraction into the membrane core. The pattern of incorporated gangliosides reflected the pattern available for incorporation. Intact synaptosomes incorporated approximately 100 pmol GM1/mg protein. Synaptosomes preincubated with proteolytic enzymes (trypsin, chymotrypsin, and papain) at different pH values (6.2, 7.4, 7.8) incorporated more exogenous gangliosides than synaptosomes preincubated in buffer alone. This effect was maximal at pH 7.8, though analysis of variance revealed that the proteolytic treatment and pH effects were probably independent processes. Overall uptake of exogenous gangliosides correlated significantly with amount of membrane protein loss, indicating that initial access of exogenous gangliosides to synaptosomal membranes is retarded by cell-surface proteins. These results suggest synaptosomes as a useful alternative to cultured cells for investigating the interaction of gangliosides with other cell surface constituents.