Bipolar manifestation of cataleptic reactions in rats

Selection of GC rats for the predisposition to cataleptic freezing has increased not only the frequency, intensity, and duration of freezing, but also the proportion of irritable or "nervous" rats with enhanced anxiety, defensive behavior with vocalization, jerky running, and jumpiness. An increased amplitude of the startle reflex is a correlate of this "nervousness." The results of the comparison of some behavioral characters in the nervous and freezing GC rats, as well as in F1 and F2 offspring from homogeneous crosses between nervous and freezing GC rats suggest that cataleptic freezing and nervousness are two poles of the same bipolar catatonic reaction. They have a common mechanism, with the alternative or preferential expression of one particular form of the reaction is determined by the external and internal environments or the set of modifier genes in the given individual.     

Bipolar Manifestation of Cataleptic Reactions in Rats

Breeding of GC rats for the predisposition to cataleptic freezing has increased not only the frequency, intensity, and duration of freezing, but also the proportion of irritable or nervous rats with enhanced anxiety, defensive behavior with vocalization, jerky running, and jumpiness. An increased amplitude of the startle reflex is a correlate of this nervousness. The results of the comparison of some behavioral characters in the nervous and freezing GC rats, as well as in S₁ and S₂ offspring from homogeneous crosses between nervous and freezing GC rats suggest that cataleptic freezing and nervousness are two poles of the same bipolar catatonic reaction. They have a common mechanism, with the alternative or preferential expression of one particular form of the reaction is determined by the external and internal environments or the set of modifier genes in the given individual.     

Combined change of behavioral traits for domestication and gene-networks in mice selectively bred for active tameness

Tameness is a major element of animal domestication and involves two components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). To understand the behavioral and genetic mechanisms of active tameness in mice, we had previously conducted selective breeding for long durations of contact and heading toward human hands in an active tameness test using a wild-derived heterogeneous stock. Although the study showed a significant increase in contacting and heading with the 12th generation of breeding, the effect on other behavioral indices related to tameness and change of gene expression levels underlying selective breeding was unclear. Here, we analyzed nine tameness-related traits at a later stage of selective breeding and analyzed how gene expression levels were changed by the selective breeding. We found that five traits, including contacting and heading, showed behavioral change in the selective groups comparing to the control through the generations. Furthermore, we conducted cluster analyses to evaluate the relationships among the nine traits and found that contacting and heading combined in an independent cluster in the selected groups, but not in the control groups. RNA-Seq of hippocampal tissue revealed differential expression of 136 genes between the selection and control groups, while the pathway analysis identified the networks associated with these genes. These results suggest that active tameness was hidden in the control groups but became apparent in the selected populations by selective breeding, potentially driven by changes in gene expression networks.     

Timing of glucocorticoid administration determines severity of lipid metabolism and behavioral effects in rats

Glucocorticoids (GCs) are a group of steroid hormones secreted by the adrenal glands in circadian cycles, and the dysregulation of GC signaling has been suggested to cause metabolic syndrome. Even though prolonged GC exposure is associated with serious side effects such as metabolic syndrome and central nervous system disorders, the use of GCs in anti-inflammatory and immunosuppressive therapies has been continuously rising. Meanwhile, the exact mechanisms by which GCs can influence the lipid metabolism as well as behavior and how they are affected by time remain unknown. In this study, the effects of two different long-term GC dosing regimens on lipid metabolism and behavior were investigated. Male Wistar rats received daily administrations of the GC dexamethasone sodium phosphate (DEX, 0.5 mg/kg body weight) at either ZT0 (Dex0) or ZT12 (Dex12). After 6 weeks of treatment, DEX-treated rats, especially those treated at ZT0, had higher hepatic lipid accumulation and serum triglyceride levels and less locomotor activity than did control rats. In addition, serum levels of corticosterone, 5-hydroxy tryptamine and norepinephrine were decreased in the Dex0 group but not in the Dex12 group compared to the control group. Furthermore, quantitative real-time polymerase chain reaction analysis indicated that the chronic administration of GCs at ZT0 upregulated genes related to glycolysis and lipid synthesis and downregulated genes related to fatty acid β-oxidation in the liver more remarkably than administration at ZT12. Both DEX-treated groups displayed severely altered expression patterns of the core clock genes Bmal1 and Per2 in the liver and in fat. In addition, the expression of glutamate aspartate transporter, glial fibrillary acidic protein and glutamate transporter-1, astrocyte-related genes important for maintaining nervous system functions, was drastically decreased in the hippocampus of DEX-treated rats, especially when DEX was given at ZT0. In conclusion, our findings confirm that the severity of side effects, indicated by altered lipid metabolism and behavioral activity, depends on the timing of GC administration and is associated with the degree of glucocorticoid receptor dysfunction after dosing at disparate time points.     

Some neuroendocrinological changes in rats of cataleptic strain GC. Influences of ontogenesis and generation of breeding

The content of biogenic amines: dopamine, noradrenaline and serotonine, in rats of cataleptic strain GC as compared with the control strain Wistar at the age of 1 and 5 months is decreased, the maximal decrease being found in the so-called "nervous" animals. The aldosterone content was decreased at 5 month age in the GC rats. The testosterone content at the age of 1 month in GC rats does not differ from that in Wistar rats, but at the age of 5 months it was decreased as compared to Wistar, the maximal decrease being found again in "nervous" GC rats. The data obtained point to peculiarities of ontogenetic regulation and to commonness of mechanisms of catalepsy and "nervousness" in GC rats.     

Systematic analysis of multigene predictors in gastric cancer exploiting gene expression signature

Gastric cancer (GC) is the second most common cause of cancer death worldwide but could be more curable if diagnosed at an earlier stage. At present, the capability to predict the efficaciousness of molecular diagnosis for GC for each patient remains elusive. The purpose of this study was to identify tumor biomarkers through systems analysis of multigene predictors exploiting the available data resource. In this study, we investigated the top 10% overexpressed genes in GC from five data sets of the Oncomine platform, with 265 GC samples versus 174 normal gastric mucosa samples. Sixteen candidate genes were identified as predictors of GC, of which 14 genes were verified through the comparison of expression levels in specimens from normal (chronic gastritis, 21 samples) and GC groups (38 samples). In addition, unique molecular portraits of diffuse adenocarcinoma (DA), intestinal adenocarcinoma (IA), and mixed adenocarcinoma (MA) were studied through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, where DA showed higher extracellular matrix alteration while IA and MA showed higher cell-cycle alteration than other types. We also found that the elevated expressions of genes during GC progression were independent of gene mutations, and high core-binding factor subunit β expression is correlated with a high overall survival rate in GC patients. Our research may provide an efficient clinical diagnosis of GC at an early stage with high accuracy and thus help improve the overall survival rate through early therapeutic interventions.     

The action of proinflammatory cytokines on formation of behavior during early postnatal ontogenesis

The study is devoted to the role of proinflammatory cytokine-interleukin-1beta during early postnatal ontogenesis in formation of behavioral programs. Cytokine was injected in pyrogenic and subpyrogenic doses during 1 week (1, 2 or 3 weeks of life). The behavior was tested in the young (40-45 days) and adult (3 months) rats in the "open field" and "elevated plus maze". The greatest behavior disordes (elevation of act's number and of motor activity, the decrease of investigation activity) are revealed in the young animals treated with IL-Ib during 1 and 3 weeks of life. These behavioral changes were marked in rats injected with pyrogenic and subpyrogenic doses of cytokine. They had a similar tendency in male and female rats. At the age of 3 months, behavior changes revealed in juvenile rats were insignificant.     

Hippocampal Gene Network Analysis in an Experimental Model of Posttraumatic Epilepsy

In the present study, we performed comprehensive gene expression and gene network analyses using a DNA microarray to elucidate the molecular events responsible for the pathology of posttraumatic epilepsy at the partial seizure stage. We used an experimental posttraumatic epilepsy model of amygdalar focal FeCl₃-injected rats and compared gene expression profiles in the hippocampus at the partial seizure stage (less than stage 3 on Racine’s convulsion scale) and that of sham-operated animals. At the partial seizure stage, upregulation of phospholipase A2 (PLA2) and lipid metabolism were observed, which have been reported to be caused by brain injury and seizures in previous studies. Furthermore, significant upregulation of genes related to inflammation and the immune system was observed. These molecular changes in PLA2 and lipid metabolism may be related to seizure propagation.     

A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.     

Behavior in the forced-swimming test and expression of BDNF and Bcl-xl genes in the rat brain

A single exposure of rats to the forced-swimming stress decreased BDNF mRNA levels in the cortex and increased Bcl-xl gene expression in the hippocampus and amygdala 24 h after the stress. The animals demonstrated a depressive-like behavior and elevated blood corticosterone level. There was a significant negative correlation between BDNF mRNA level in the cortex and immobility time during swimming. Repeated exposure to swimming stress caused the elevation of the hippocampal BDNF mRNA level assessed 24 h after the second swimming session. The data suggest that stress-induced down-regulation of cortical BDNF gene expression and behavioral despair in the forced-swimming test may be interrelated. The increase in the BDNF and Bcl-xl mRNA levels may contribute to the mechanisms protecting the brain against negative effects of stress.     

Regulated genes in mesenchymal stem cells and gastric cancer

AIM: To investigate the genes regulated in mesenchymal stem cells(MSCs) and diffuse-type gastric cancer(GC),gene expression was analyzed. METHODS: Gene expression of MSCs and diffuse-type GC cells were analyzed by microarray. Genes related to stem cells, cancer and the epithelial-mesenchymal transition(EMT) were extracted from human gene lists using Gene Ontology and reference information. Gene panels were generated, and messenger RNA gene expression in MSCs and diffuse-type GC cells was analyzed. Cluster analysis was performed using the NCSS software.RESULTS: The gene expression of regulator of G-protein signaling 1(RGS1) was up-regulated in diffuse-type GC cells compared with MSCs. A panel of stem-cell related genes and genes involved in cancer or the EMT were examined. Stem-cell related genes, such as growth arrest-specific 6, musashi RNA-binding protein 2 and hairy and enhancer of split 1(Drosophila), NOTCH family genes and Notch ligands, such as delta-like 1(Drosophila) and Jagged 2, were regulated.CONCLUSION: Expression of RGS1 is up-regulated, and genes related to stem cells and NOTCH signaling are altered in diffuse-type GC compared with MSCs.     

Isolation of an early neural maker gene abundantly expressed in the nervous system of the ascidian, Halocynthia roretzi

Ascidian tadpole larvae possess a primitive nervous system, which is a prospective prototype of the chordate nervous system. It is composed of relatively few cells but sufficient for complex larval behavior. Here we report on HrETR-1, a gene zygotically expressed in a large proportion of the developing neural cells of the ascidian, Halocynthia roretzi. HrETR-1 is an early neural marker which can be used for analyzing neural differentiation. HrETR-1 expression intensified in most neural cells of genes isolated to date, in both central and peripheral nervous systems including palps as early as the 110-cell stage. Using this gene as a probe, we characterized neural cells in the nervous system as well as confirming their origins. Also, we recognized three types of peripheral epidermal neurons which presumably correlate to the larval neurons previously reported for another ascidian. Among these, five bilateral neurons located in the anterior region of the trunk appeared to be derived from a8.26 blastomeres.     

Age-related changes of Renin-Angiotensin system genes in white adipose tissue of rats.

The adipose tissue renin-angiotensin system has been implicated in the regulation of adipocyte growth and differentiation. We studied the influence of age, body weight, total body fat content, anatomical localization, and diet on the expression of angiotensinogen (AGT) and angiotensin II type 1 (AT 1 )-receptor genes in white adipose tissue of normal and postnatal overfed rats. Relative gene expression was measured in epididymal adipose tissue and liver of control and postnatal overfed (PNO) rats at the age of 4, 8, and 12 weeks using real time RT-PCR. Body fat content was determined by carcass analysis. Body weight and body fat content were only significantly greater in PNO rats when compared to control rats at the age of 4 weeks. At the age of 12 weeks, AGT expression was significantly decreased in both tissues. Furthermore, expression of the AT 1 -receptor gene was significantly decreased in liver but not in adipose tissue at 12 weeks of age. Postnatal overfeeding did not influence the expression levels of either gene at any time-point in either liver or adipose tissue. At the age of 24 weeks, AGT expression was significantly greater in epididymal than in subcutaneous adipose tissue, whereas no site-specific differences could be found for the AT 1 -receptor. We conclude that age and depot-specific mechanisms are of more importance for the expression of AGT and AT 1 -receptor genes during the first 12 weeks of age than a short period of overfeeding.     

The role of the orbital cortex in feeding behavior]

It has been found that extirpation of the orbital zones of the cerebral cortex in dogs in which the structures of the limbic and striate levels of nervous integration were previously ablated, produced more profound disturbances of the higher nervous activity than the previous operations. Not only conditioned positive and inhibitory reactions were affected, but unconditioned alimentary reflexes as well, while food motivation sharply decreased. Further experiments on the operated animals and could go on, only when alimentary excitability was enhanced. A conclusion has been drawn that the orbital zones of the cerebral cortex are directly related to the achievement of an integrated alimentary behavioral reaction.