Analysis Of Brain Gene Expression Research Articles

Microbiota influence on behavior: Integrative analysis of serotonin metabolism and behavioral profile in germ-free mice.

Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety-like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared with CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared with CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota-mediated regulation. While no impact of GF status on brain 5-HT was observed, substantial differences in gut 5-HT metabolism were noted, with tissue-dependent results indicating a varying role of microbiota along the GI tract.

CXCL13 Neutralization Attenuates Neuropsychiatric Manifestations in Lupus-Prone Mice

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target.

Postnatal exposure to low doses of Chlorpyrifos induces long-term effects on 5C-SRTT learning and performance, cholinergic and GABAergic systems and BDNF expression

Alterations in attention and inhibitory control are common features in several neurological disorders. Environmental factors such as exposure to pesticides have been linked to their appearance. Chlorpyrifos (CPF) is one of the most widely used organophosphate compounds in the world. CPF exposure during development seems to be critical for later behavioral and molecular disruptions during adult ages, although this depends on the specific period of development, where the preweaning period is one of the least studied. Despite the abundant empirical work made in the last decades on developmental CPF exposure, the systematic study of this on attention is sparse, and nonexistent concerning inhibitory control, without a single study on preweaning developmental stages. The present research explored the effects of the exposure to low doses of CPF that do not elicit a significant inhibition of the Cholinesterases during this developmental period on rats' behavior in the five-choice serial reaction time task. Behavioral manipulations (inter-trial interval and stimulus duration), pharmacological manipulations (cholinergic and GABAergic drugs) and brain gene expression analyses were also conducted. Exposure to CPF decreased the locomotor activity and enhanced the learning profile of the female rats, increased the impulsive rates, unmasked by a longer inter-trial interval, hypo-sensitized the cholinergic system and down-regulated the mRNA expression levels of the brain-derived neurotrophic factor in the dorsal striatum of the male rats. This happened without significant inhibition of the brain Acetylcholinesterase. All this new information corroborates that the exposure to a common pesticide at low doses during a key, but under-explored developmental period importantly affects different behaviors, neurotransmitter systems, and molecules that are altered in the main neurological disorders observed nowadays.

Behavior-dependent cis regulation reveals genes and pathways associated with bower building in cichlid fishes

Many behaviors are associated with heritable genetic variation [Kendler and Greenspan (2006) Am J Psychiatry 163:1683-1694]. Genetic mapping has revealed genomic regions or, in a few cases, specific genes explaining part of this variation [Bendesky and Bargmann (2011) Nat Rev Gen 12:809-820]. However, the genetic basis of behavioral evolution remains unclear. Here we investigate the evolution of an innate extended phenotype, bower building, among cichlid fishes of Lake Malawi. Males build bowers of two types, pits or castles, to attract females for mating. We performed comparative genome-wide analyses of 20 bower-building species and found that these phenotypes have evolved multiple times with thousands of genetic variants strongly associated with this behavior, suggesting a polygenic architecture. Remarkably, F1 hybrids of a pit-digging and a castle-building species perform sequential construction of first a pit and then a castle bower. Analysis of brain gene expression in these hybrids showed that genes near behavior-associated variants display behavior-dependent allele-specific expression with preferential expression of the pit-digging species allele during pit digging and of the castle-building species allele during castle building. These genes are highly enriched for functions related to neurodevelopment and neural plasticity. Our results suggest that natural behaviors are associated with complex genetic architectures that alter behavior via cis-regulatory differences whose effects on gene expression are specific to the behavior itself.

Brain gene expression analyses in virgin and mated queens of fire ants reveal mating-independent and socially regulated changes.

Transcriptomes of dissected brains from virgin alate and dealate mated queens from polygyne fire ants (Solenopsis invicta) were analyzed and compared. Thirteen genes were upregulated in mated queen brain, and nine were downregulated. While many of the regulated genes were either uncharacterized or noncoding RNAs, those annotated genes included two hexamerin proteins, astakine neuropeptide, serine proteases, and serine protease inhibitors. We found that for select differentially expressed genes in the brain, changes in gene expression were most likely driven by the changes in physiological state (i.e., age, nutritional status, or dominance rank) or in social environment (released from influence of primer pheromone). This was concluded because virgins that dealated after being separated from mated queens showed similar patterns of gene expression in the brain as those of mated queens for hexamerin 1, astakine, and XR_850909. Abaecin (XR_850725), however, appears upregulated only after mating. Therefore, our findings contribute to distinguish how specific gene networks, especially those influenced by queen primer pheromone, are regulated in queen ants. Additionally, to identify brain signaling pathways, we mined the fire ant genome and compiled a list of G‐protein‐coupled receptors (GPCRs). The expression level of GPCRs and other genes in the “genetic toolkit” in the brains of virgin alates and mated dealate queens is reported.

Sequential social experiences interact to modulate aggression but not brain gene expression in the honey bee (Apis mellifera)

BackgroundIn highly structured societies, individuals behave flexibly and cooperatively in order to achieve a particular group-level outcome. However, even in social species, environmental inputs can have long lasting effects on individual behavior, and variable experiences can even result in consistent individual differences and constrained behavioral flexibility. Despite the fact that such constraints on behavior could have implications for behavioral optimization at the social group level, few studies have explored how social experiences accumulate over time, and the mechanistic basis of these effects. In the current study, I evaluate how sequential social experiences affect individual and group level aggressive phenotypes, and individual brain gene expression, in the highly social honey bee (Apis mellifera). To do this, I combine a whole colony chronic predator disturbance treatment with a lab-based manipulation of social group composition.ResultsCompared to the undisturbed control, chronically disturbed individuals show lower aggression levels overall, but also enhanced behavioral flexibility in the second, lab-based social context. Disturbed bees display aggression levels that decline with increasing numbers of more aggressive, undisturbed group members. However, group level aggressive phenotypes are similar regardless of the behavioral tendencies of the individuals that make up the group, suggesting a combination of underlying behavioral tendency and negative social feedback influences the aggressive behaviors displayed, particularly in the case of disturbed individuals. An analysis of brain gene expression showed that aggression related biomarker genes reflect an individual’s disturbance history, but not subsequent social group experience or behavioral outcomes.ConclusionsIn highly social animals with collective behavioral phenotypes, social context may mask underlying variation in individual behavioral tendencies. Moreover, gene expression patterns may reflect behavioral tendency, while behavioral outcomes are further regulated by social cues perceived in real-time.

Dynamic changes in social dominance and mPOA GnRH expression in male mice following social opportunity

Social competence - the ability of animals to dynamically adjust their social behavior dependent on the current social context – is fundamental to the successful establishment and maintenance of social relationships in group-living species. The social opportunity paradigm, where animals rapidly ascend a social hierarchy following the removal of more dominant individuals, is a well-established approach for studying the neural and neuroendocrine mechanisms underlying socially competent behavior. In the current study, we demonstrate that this paradigm can be successfully adapted for studying socially competent behavior in laboratory mice. Replicating our previous reports, we show that male laboratory mice housed in a semi-natural environment form stable linear social hierarchies. Novel to the current study, we find that subdominant male mice immediately respond to the removal of the alpha male from a hierarchy by initiating a dramatic increase in aggressive behavior towards more subordinate individuals. Consequently, subdominants assume the role of the alpha male. Analysis of brain gene expression in individuals 1h following social ascent indicates elevated gonadotropin-releasing hormone (GnRH) mRNA levels in the medial preoptic area (mPOA) of the hypothalamus compared to individuals that do not experience a social opportunity. Moreover, hormonal analyses indicate that subdominant individuals have increased circulating plasma testosterone levels compared to subordinate individuals. Our findings demonstrate that male mice are able to dynamically and rapidly adjust both behavior and neuroendocrine function in response to changes in social context. Further, we establish the social opportunity paradigm as an ethologically relevant approach for studying social competence and behavioral plasticity in mammals.

Photoperiodic Modulation of Circadian Clock and Reproductive Axis Gene Expression in the Pre-Pubertal European Sea Bass Brain.

The acquisition of reproductive competence requires the activation of the brain-pituitary-gonad (BPG) axis, which in most vertebrates, including fishes, is initiated by changes in photoperiod. In the European sea bass long-term exposure to continuous light (LL) alters the rhythm of reproductive hormones, delays spermatogenesis and reduces the incidence of precocious males. In contrast, an early shift from long to short photoperiod (AP) accelerates spermatogenesis. However, how photoperiod affects key genes in the brain to trigger the onset of puberty is still largely unknown. Here, we investigated if the integration of the light stimulus by clock proteins is sufficient to activate key genes that trigger the BPG axis in the European sea bass. We found that the clock genes clock, npas2, bmal1 and the BPG genes gnrh, kiss and kissr share conserved transcription factor frameworks in their promoters, suggesting co-regulation. Other gene promoters of the BGP axis were also predicted to be co-regulated by the same frameworks. Co-regulation was confirmed through gene expression analysis of brains from males exposed to LL or AP photoperiod compared to natural conditions: LL fish had suppressed gnrh1, kiss2, galr1b and esr1, while AP fish had stimulated npas2, gnrh1, gnrh2, kiss2, kiss1rb and galr1b compared to NP. It is concluded that fish exposed to different photoperiods present significant expression differences in some clock and reproductive axis related genes well before the first detectable endocrine and morphological responses of the BPG axis.

Preventive Effect of Soybean on Brain Aging and Amyloid-β Accumulation: Comprehensive Analysis of Brain Gene Expression.

The expected prevalence of Alzheimer's disease (AD), the most common neurodegenerative disease triggered by aging, has become a critical problem. Although the cause is clear, accumulation of amyloid-β (Aβ), we still cannot totally cure this disease. Hence, it is essential to prevent the symptoms that have appeared. A number of studies have reported that soybean supplementation prevents cognitive dysfunction. Besides being a rich source of vegetable proteins, soybean contains other functional ingredients such as phytoestrogens, oligosaccharides, and dietary fibers. Especially, recent studies suggested greater functions with green soybean. Comprehensive analysis of gene expression in the brains of mice that ingested soybean using high-density oligonucleotide microarray suggests that an increase of an endogenous Aβ-chaperone, lipocalin-type prostaglandin D2 synthase (Ptgds), leads to suppressed Aβ accumulation, resulting in the prevention of cognitive dysfunction. Here we will review relevant patents and estimated effective components and underlying mechanisms of soybeans, suggested by comparing effects of green and yellow soybean breeds to mice.

CCR5 knockout prevents neuronal injury and behavioral impairment induced in a transgenic mouse model by a CXCR4-using HIV-1 glycoprotein 120.

The innate immune system has been implicated in several neurodegenerative diseases, including HIV-1-associated dementia. In this study, we show that genetic ablation of CCR5 prevents microglial activation and neuronal damage in a transgenic model of HIV-associated brain injury induced by a CXCR4-using viral envelope gp120. The CCR5 knockout (KO) also rescues spatial learning and memory in gp120-transgenic mice. However, the CCR5KO does not abrogate astrocytosis, indicating it can occur independently from neuronal injury and behavioral impairment. To characterize further the neuroprotective effect of CCR5 deficiency we performed a genome-wide gene expression analysis of brains from HIVgp120tg mice expressing or lacking CCR5 and nontransgenic controls. A comparison with a human brain microarray study reveals that brains of HIVgp120tg mice and HIV patients with neurocognitive impairment share numerous differentially regulated genes. Furthermore, brains of CCR5 wild-type and CCR5KO gp120tg mice express markers of an innate immune response. One of the most significantly upregulated factors is the acute phase protein lipocalin-2 (LCN2). Using cerebrocortical cell cultures, we find that LCN2 is neurotoxic in a CCR5-dependent fashion, whereas inhibition of CCR5 alone is not sufficient to abrogate neurotoxicity of a CXCR4-using gp120. However, the combination of pharmacologic CCR5 blockade and LCN2 protects neurons from toxicity of a CXCR4-using gp120, thus recapitulating the finding in CCR5-deficient gp120tg mouse brain. Our study provides evidence for an indirect pathologic role of CCR5 and a novel protective effect of LCN2 in combination with inhibition of CCR5 in HIV-associated brain injury.

Bioinformatics Analyses Reveal Age-Specific Neuroimmune Modulation as a Target for Treatment of High Ethanol Drinking

Use of in silico bioinformatics analyses has led to important leads in the complex nature of alcoholism at the genomic, epigenomic, and proteomic level, but has not previously been successfully translated to the development of effective pharmacotherapies. In this study, a bioinformatics approach led to the discovery of neuroimmune pathways as an age-specific druggable target. Minocycline, a neuroimmune modulator, reduced high ethanol (EtOH) drinking in adult, but not adolescent, mice as predicted a priori. Age and sex-divergent effects in alcohol consumption were quantified in FVB/NJ×C57BL/6J F1 mice given access to 20% alcohol using a 4h/d, 4-day drinking-in-dark (DID) paradigm. In silico bioinformatics pathway overrepresentation analysis for age-specific effects of alcohol in brain was performed using gene expression data collected in control and DID-treated, adolescent and adult, male mice. Minocycline (50mg/kg i.p., once daily) or saline alone was tested for an effect on EtOH intake in the F1 and C57BL/6J (B6) mice across both age and gender groups. Effects of minocycline on the pharmacokinetic properties of alcohol were evaluated by comparing the rates of EtOH elimination between the saline- and minocycline-treated F1 and B6 mice. Age and gender differences in DID consumption were identified. Only males showed a clear developmental increase difference in drinking over time. In silico analyses revealed neuroimmune-related pathways as significantly overrepresented in adult, but not in adolescent, male mice. As predicted, minocycline treatment reduced drinking in adult, but not adolescent, mice. The age effect was present for both genders, and in both the F1 and B6 mice. Minocycline had no effect on the pharmacokinetic elimination of EtOH. Our results are a proof of concept that bioinformatics analysis of brain gene expression can lead to the generation of new hypotheses and a positive translational outcome for individualized pharmacotherapeutic treatment of high alcohol consumption.

Computational neuroanatomy and co-expression of genes in the adult mouse brain, analysis tools for the Allen Brain Atlas

We review quantitative methods and software developed to analyze genome-scale, brain-wide spatially-mapped gene-expression data. We expose new methods based on the underlying high-dimensional geometry of voxel space and gene space, and on simulations of the distribution of co-expression networks of a given size. We apply them to the Allen Atlas of the adult mouse brain, and to the coexpression network of a set of genes related to nicotine addiction retrieved from the NicSNP database. The computational methods are implemented in BrainGeneExpressionAnalysis (BGEA), a Matlab toolbox available for download.

Genome-wide microarray analysis of brain gene expression in mice on a short-term high iron diet

The effects of systemic iron overload on the brain are unclear. Microarray analysis of brain gene expression in mice following short-term iron supplementation revealed altered expression of 287 genes, although most changes were small. Transcripts for the iron storage protein ferritin light chain increased 20% ( p = 0.002) and transcripts for iron regulatory protein 1, which negatively regulates ferritin translation, decreased 28% ( p = 0.048). There were expression changes for genes involved in important brain functions such as neurotransmission and nitric oxide signaling, which is dependent on iron. Few changes related to reactive oxygen species, inflammation or apoptosis, however expression changes were observed for genes causatively linked to neurological disorders, including Charcot-Marie-Tooth disease, neuronal ceroid lipofuscinosis and mucolipidosis. The latter involve intralysosomal lipofuscin build-up that may reflect lysosomal iron accumulation. The findings suggest that high iron intake may cause subtle brain effects of clinical relevance in some circumstances.

Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression.

BackgroundMost studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations.Methodology/Principal FindingsWe performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data.Conclusions/SignificanceThe observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions.

Evo-Devo and the Evolution of Social Behavior: Brain Gene Expression Analyses in Social Insects

Studies of genes and social behavior, aided by new genomic resources, are coming of age. Here, we show how some of the insights that have emerged from research on the evolution of development (evo-devo) also provide a useful framework for studying the evolution of social behavior at the molecular level. These insights include co-opting old genes for new functions, phenotypic modularity, genetic tool kits, the importance of gene regulation in evolutionary change, and the influences of some genes over multiple timescales. We next outline a few differences between development and behavior that pose challenges for an evo-devo approach to behavior. For the remainder of this chapter, we review several studies that illustrate the relevance of evo-devo insights to our understanding of the evolution of behaviors related to eusociality in the insect societies.

Patterns of gene expression in the limbic system of suicides with and without major depression

The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides=18, non depressed suicides=8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

Species differences in brain gene expression profiles associated with adult behavioral maturation in honey bees

BackgroundHoney bees are known for several striking social behaviors, including a complex pattern of behavioral maturation that gives rise to an age-related colony division of labor and a symbolic dance language, by which successful foragers communicate the location of attractive food sources to their nestmates. Our understanding of honey bees is mostly based on studies of the Western honey bee, Apis mellifera, even though there are 9–10 other members of genus Apis, showing interesting variations in social behavior relative to A. mellifera. To facilitate future in-depth genomic and molecular level comparisons of behavior across the genus, we performed a microarray analysis of brain gene expression for A. mellifera and three key species found in Asia, A. cerana, A. florea and A. dorsata.ResultsFor each species we compared brain gene expression patterns between foragers and adult one-day-old bees on an A. mellifera cDNA microarray and calculated within-species gene expression ratios to facilitate cross-species analysis. The number of cDNA spots showing hybridization fluorescence intensities above the experimental threshold was reduced by an average of 16% in the Asian species compared to A. mellifera, but an average of 71% of genes on the microarray were available for analysis. Brain gene expression profiles between foragers and one-day-olds showed differences that are consistent with a previous study on A. mellifera and were comparable across species. Although 1772 genes showed significant differences in expression between foragers and one-day-olds, only 218 genes showed differences in forager/one-day-old expression between species (p < 0.001). Principal Components Analysis revealed dominant patterns of expression that clearly distinguished between the four species but did not reflect known differences in behavior and ecology. There were species differences in brain expression profiles for functionally related groups of genes.ConclusionWe conclude that the A. mellifera cDNA microarray can be used effectively for cross-species comparisons within the genus. Our results indicate that there is a widespread conservation of the molecular processes in the honey bee brain underlying behavioral maturation. Species differences in brain expression profiles for functionally related groups of genes provide possible clues to the basis of behavioral variation in the genus.

Implication of SSAT by Gene Expression and Genetic Variation in Suicide and Major Depression

A large body of evidence suggests that predisposition to suicide, an important public health problem, is mediated to a certain extent by neurobiological factors. To investigate patterns of expression in suicide with and without major depression and to identify new molecular targets that may play a role in the neurobiology of these conditions. Brain gene expression analysis was performed using the Affymetrix HG-U133 chipset in the orbital cortex (Brodmann area [BA] 11), the dorsolateral prefrontal cortex (BA8/9), and motor cortex (BA4). Subsequent studies were carried out in independent samples from adjacent areas to validate positive findings, confirm their relevance at the protein level, and investigate possible effects of genetic variation. We investigated 12 psychiatrically normal control subjects and 24 suicide victims, including 16 with and 8 without major depression, in the brain gene expression analysis, validation, and protein studies. The genetic studies included 181 suicide completers and 80 psychiatrically normal controls. All subjects investigated were male and of French Canadian origin. Gene expression measures from microarray, semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses. Twenty-six genes were selected because of the consistency of their expression pattern (fold change, >1.3 in either direction [P<or=.01] in at least 2 regions). The spermine/spermidine N(1)-acetyltransferase gene (SSAT) was successfully validated by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses. A variant located in the SSAT polyamine-responsive element regulatory region (SSAT342A/C) demonstrated a significant effect of genotype on SSAT brain expression levels (F(1) = 5.34; P = .02). Further investigation of this variant in an independent sample of 181 male suicide completers and 80 male controls showed a higher frequency of the SSAT342C allele among suicide cases (odds ratio, 2.7; 95% confidence interval, 1.4-5.3; P = .005), suggesting that this allele may increase predisposition to suicide. These data suggest a role for SSAT, the rate-limiting enzyme in the catabolism of polyamines, in suicide and depression and a role for the SSAT342 locus in the regulation of SSAT gene expression.

Microarray analysis of brain gene expression in human alcoholism

Microarray analysis of brain gene expression in human alcoholism

Analysis of brain gene expression in schizophrenia by molecular cloning techniques

The paper describes an investigation of some possible “dimensional” systems for the designation of physical concepts. The usual system, based on the primary concepts of length, mass, and time, results in a large number of ambiguities (Table II) and is therefore unsatisfactory. The introduction of an additional primary concept for heat and another for electromagnetism is an improvement, but many ambiguities still remain (Table III). The trouble is caused by our failure to distinguish between distances in different directions.By introducing two fundamental lengths lr and lt (radial and tangential) in place of the usual l, we eliminate the former difficulty and obtain distinct designation symbols for the concepts of energy and torque, for normal stress and shear stress, for pharosage (radiant energy per unit area) and hellos (brightness).There are six types of practical application for idon theory (“dimensions”), all of which are handled as well (or better) by the lr,lt-system as by the old method. Examples are given of the use of the new method in checking equations and in deriving new equations by idonic analysis. Tables of designation symbols are given for the principal concepts of physics (Table VI to X). Finally, an alternative system is outlined which employes the fundamental lengths lr, lt, and l, and which discriminates between vectors and scalars in physical space (Table XI). This vector system is useful in certain problems, though in most cases the simpler lr/lt-system is adequate.