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Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear  [PDF]
Kwang H. Choi, Thien Le, Jennifer McGuire, Jennifer Coyner, Brandon W. Higgs, Suad Diglisic, Luke R. Johnson, David M. Benedek, Robert J. Ursano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049183
Abstract: A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.
Sweet Success, Bitter Defeat: A Taste Phenotype Predicts Social Status in Selectively Bred Rats  [PDF]
John M. Eaton, Nancy K. Dess, Clinton D. Chapman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046606
Abstract: For social omnivores such as rats and humans, taste is far more than a chemical sense activated by food. By virtue of evolutionary and epigenetic elaboration, taste is associated with negative affect, stress vulnerability, responses to psychoactive substances, pain, and social judgment. A crucial gap in this literature, which spans behavior genetics, affective and social neuroscience, and embodied cognition, concerns links between taste and social behavior in rats. Here we show that rats selectively bred for low saccharin intake are subordinate to high-saccharin-consuming rats when they compete in weight-matched dyads for food, a task used to model depression. Statistical and experimental controls suggest that differential resource utilization within dyads is not an artifact of individual-level processes such as apparatus habituation or ingestive motivation. Tail skin temperature measurements showed that LoS rats display larger hyperthermic responses to social interaction after status is established, evidence linking taste, social stress, autonomic reactivity, and depression-like symptoms. Based on regression using early- and late-competition predictors to predict dyadic disparity in final competition scores, we tentatively suggest that HiS rats emerge as dominant both because of an “early surge” on their part and because LoS acquiesce later. These findings should invigorate the comparative study of individual differences in social status and its relationship to mental and physical health.
Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety  [PDF]
Yi-Chun Yen,Elmira Anderzhanova,Rainer Landgraf,Carsten T. Wotjak
Frontiers in Behavioral Neuroscience , 2013, DOI: 10.3389/fnbeh.2013.00103
Abstract: We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique and overlapping endophenotypes of the three diseases. To this end Venn diagrams were used as an instrument for discrimination of possible models. We arranged the endophenotypes in Venn diagrams and translated them into different behavioral tests. LAB mice showed elevated levels of locomotion in the open field (OF) test with deficits in habituation, compared to mice bred for normal (NAB) and high anxiety-related behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice resulted in offspring showing a low level of locomotion comparable to HAB mice, indicating that the HAB alleles are dominant over LAB alleles in determining the level of locomotion. In a holeboard test, LAB mice spent less time in hole exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice displayed no impairments in social interaction and prepulse inhibition (PPI), implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB mice displayed hyperarousal, active coping styles, and cognitive deficits, symptoms shared by mania and ADHD, they failed to reveal the classic manic endophenotypes, such as increased hedonia and object interaction. The neuroleptic haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer lithium and the psychostimulant amphetamine, in contrast, selectively reduced hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles, LAB mice are suggested as a novel rodent model of ADHD-like symptoms.
Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait  [PDF]
Amanda L. Schott, Betty Zimmerberg
Pharmacology & Pharmacy (PP) , 2014, DOI: 10.4236/pp.2014.59096

Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.

Skeletal Muscle Characterization of Japanese Quail Line Selectively Bred for Lower Body Weight as an Avian Model of Delayed Muscle Growth with Hypoplasia  [PDF]
Young Min Choi, Yeunsu Suh, Sangsu Shin, Kichoon Lee
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095932
Abstract: This study was designed to extensively characterize the skeletal muscle development in the low weight (LW) quail selected from random bred control (RBC) Japanese quail in order to provide a new avian model of impaired and delayed growth in physically normal animals. The LW line had smaller embryo and body weights than the RBC line in all age groups (P<0.05). During 3 to 42 d post-hatch, the LW line exhibited approximately 60% smaller weight of pectoralis major muscle (PM), mainly resulting from lower fiber numbers compared to the RBC line (P<0.05). During early post-hatch period when myotubes are still actively forming, the LW line showed impaired PM growth with prolonged expression of Pax7 and lower expression levels of MyoD, Myf-5, and myogenin (P<0.05), likely leading to impairment of myogenic differentiation and consequently, reduced muscle fiber formation. Additionally, the LW line had delayed transition of neonatal to adult myosin heavy chain isoform, suggesting delayed muscle maturation. This is further supported by the finding that the LW line continued to grow unlike the RBC line; difference in the percentages of PMW to body weights between both quail lines diminished with increasing age from 42 to 75 d post-hatch. This delayed muscle growth in the LW line is accompanied by higher levels of myogenin expression at 42 d (P<0.05), higher percentage of centered nuclei at 42 d (P<0.01), and greater rate of increase in fiber size between 42 and 75 d post-hatch (P<0.001) compared to the RBC line. Analysis of physiological, morphological, and developmental parameters during muscle development of the LW quail line provided a well-characterized avian model for future identification of the responsible genes and for studying mechanisms of hypoplasia and delayed muscle growth.
A brain microdialysis study on 5-HT release in freely moving rat lines selectively bred for differential 5-HT1A receptor function
Gonzalez, L.E.;Parada, M.A.;Tucci, S.;Teneud, L.;Overstreet, D.H.;Hernandez, L.;
Brazilian Journal of Medical and Biological Research , 2003, DOI: 10.1590/S0100-879X2003000200014
Abstract: breeding for high and low hypothermic responses to systemic administration of a serotonin1a (5-ht1a) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-oh-dpat) has resulted in high dpat-sensitive (hds) and low dpat-sensitive (lds) lines of rats, respectively. these lines also differ in several behavioral measures associated with stress. in the present microdialysis study we observed that basal 5-ht concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between hds and lds rats. thus, behavioral differences between the hds and lds lines might not be attributed to differences in basal 5-ht release. however, both lines had lower basal levels of 5-ht release than their randomly bred control group (random dpat-sensitive, rds) in the prefrontal cortex (mean ± sem, pg/20 μl, was 3.0 ± 0.4 for lds, 3.8 ± 0.3 for hds and 6.4 ± 0.6 for rds; f(2,59) = 5.8, p<0.005). the administration of (±)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-ht levels in hds rats (500%) as compared with lds (248%) or rds (243%) rats (p<0.0001). there were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-ht increase of about 900% in the three groups. this differential response to fenfluramine may be due to functional alterations of hippocampal 5-ht reuptake sites in the hds line.
A brain microdialysis study on 5-HT release in freely moving rat lines selectively bred for differential 5-HT1A receptor function  [cached]
Gonzalez L.E.,Parada M.A.,Tucci S.,Teneud L.
Brazilian Journal of Medical and Biological Research , 2003,
Abstract: Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean ± SEM, pg/20 μl, was 3.0 ± 0.4 for LDS, 3.8 ± 0.3 for HDS and 6.4 ± 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (±)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500%) as compared with LDS (248%) or RDS (243%) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900% in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line.
Disaccharide intolerance  [PDF]
Radlovi? Nedeljko
Srpski Arhiv za Celokupno Lekarstvo , 2010, DOI: 10.2298/sarh1012777r
Abstract: Disaccharide intolerance presents a pathogenic heterogeneous and most complex clinical entity. It usually occurs due to primary or secondary deficit of disaccharide activity, and rarely because of disorders of absorption or monomer metabolism. Symptomatology of disaccharide maldigestion and/or malabsorption depends on the severity of the basic disorder, the level of its overload and the patient’s age. In the youngest children, due to a rapid gastrointestinal transit and a low compensatory capacity of the colon, osmotic-fermentative diarrhoea forms the basis of clinical features. Diarrhoeal disorder can be occasionally so intensive that it disturbs not only water and electrolytic balance, but also the nutritive status of the child. In older children and adults, as well as in milder forms of the disorder, the symptomatology, most often without diarrhoea, is dominated by abdominal colic, loud peristaltic sounds, meteorism and increased flatulence. Metabolic disorders followed by conversion disorders of galactose and fructose into glucose are characterized by a hypoglycaemic crisis, as well as by various multisystemic damages due to the deposit of toxic metabolic products. The diagnosis of gastrointestinal forms of disaccharide intolerance is based on the pathologic clinical and laboratory response during the overload test, while that of the metabolic form is based on the confirmed presence of specific enzyme and/or genetic defect. Treatment of disaccharide intolerance is based on the elimination diet. Besides, in the secondary forms of the disorder, it is also necessary to apply the treatment of the basic disease.
Different Patterns of Respiration in Rat Lines Selectively Bred for High or Low Anxiety  [PDF]
Luca Carnevali, Andrea Sgoifo, Mimosa Trombini, Rainer Landgraf, Inga D. Neumann, Eugene Nalivaiko
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064519
Abstract: In humans, there is unequivocal evidence of an association between anxiety states and altered respiratory function. Despite this, the link between anxiety and respiration has been poorly evaluated in experimental animals. The primary objective of the present study was to investigate the hypothesis that genetic lines of rats that differ largely in their anxiety level would display matching alterations in respiration. To reach this goal, respiration was recorded in high-anxiety behavior (HAB, n = 10) and low-anxiety behavior (LAB, n = 10) male rats using whole-body plethysmography. In resting state, respiratory rate was higher in HABs (85±2 cycles per minute, cpm) than LABs (67±2 cpm, p<0.05). During initial testing into the plethysmograph and during a restraint test, HAB rats spent less time at high-frequency sniffing compared to LAB rats. In addition, HAB rats did not habituate in terms of respiratory response to repetitive acoustic stressful stimuli. Finally, HAB rats exhibited a larger incidence of sighs during free exploration of the plethysmograph and under stress conditions. We conclude that: i) HAB rats showed respiratory changes (elevated resting respiratory rate, reduced sniffing in novel environment, increased incidence of sighs, and no habituation of the respiratory response to repetitive stimuli) that resemble those observed in anxious and panic patients, and ii) respiratory patterns may represent a promising way for assessing anxiety states in preclinical studies.
Study on Delaunay Triangulation with the Islets Constraints  [PDF]
Dong Wei, Xinghua Liu
Intelligent Information Management (IIM) , 2010, DOI: 10.4236/iim.2010.26045
Abstract: Aiming at Delaunay triangulation with islets constrains in terrain simulation. A general Delaunay triangulation algorithm for constrained data set with islets is proposed. The algorithm firstly constructs Constrained Delaunay Triangulation with constraint polygons which are inner boundary of islets, then according to topological relations within edge, surface, arc segment, applies bidirectional search to find the triangle in islet, lastly it carries on certain corresponding processing to complete the Delaunay triangulation algorithm with islets. The analyses show the algorithm simple, fast speed. The algorithm can be used in 3-D terrain vision.
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