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Genes, Brain, and Behavior

David R Goulding, Viktoriya D Nikolova, Lopa Mishra, Lisheng Zhuo, Koji Kimata, Sandra J McBride, Sheryl S Moy, G Jean Harry, Stavros Garantziotis
In recent years, several genome-wide association studies have identified candidate regions for genetic susceptibility in major mood disorders. Most notable are regions in a locus in chromosome 3p21, encompassing the genes NEK4-ITIH1-ITIH3-ITIH4. Three of these genes represent heavy chains of the composite protein inter-α-inhibitor (IαI). In order to further establish associations of these genes with mood disorders, we evaluated behavioral phenotypes in mice deficient in either Ambp/bikunin, which is necessary for functional ITIH1 and ITIH3 complexes, or in Itih4, the gene encoding the heavy chain Itih4...
July 10, 2018: Genes, Brain, and Behavior
Xaquín Gurriarán, Julio Rodríguez-López, Gerardo Flórez, César Pereiro, José Manuel Fernández, Emilio Fariñas, Valentín Estévez, Manuel Arrojo, Javier Costas
Genetic susceptibility to substance use disorders (SUDs) is partially shared between substances. Heritability of any substance dependence, estimated as 54%, is partly explained by additive effects of common variants. Comorbidity between SUDs and other psychiatric disorders is frequent. The present study aims to analyze the additive role of common variants in this comorbidity using polygenic scores (PGSs) based on genome-wide association study (GWAS) discovery samples of schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, major depressive disorder, and anxiety disorders, available from large consortia...
July 4, 2018: Genes, Brain, and Behavior
Michael C Saul, Charles Blatti, Wei Yang, Syed Abbas Bukhari, Hagai Y Shpigler, Joseph M Troy, Christopher H Seward, Laura Sloofman, Sriram Chandrasekaran, Alison M Bell, Lisa Stubbs, Gene E Robinson, Sihai Dave Zhao, Saurabh Sinha
Social challenges like territorial intrusions evoke behavioral responses in widely diverging species. Recent work has revealed that evolutionary "toolkits" - genes and modules with lineage-specific variations but deep conservation of function - participate in the behavioral response to social challenge. Here, we develop a multi-species computational-experimental approach to characterize such a toolkit at a systems level. Brain transcriptomic responses to social challenge was probed via RNA-seq profiling in three diverged species - honey bees, mice, and three-spined stickleback fish - following a common methodology, allowing fair comparisons across species...
July 2, 2018: Genes, Brain, and Behavior
Tingsong Li, Min Cheng, Juan Wang, Siqi Hong, Mei Li, Shuang Liao, Lingling Xie, Yajun Qin, Li Jiang
OBJECTIVE: To detect syntaxin-binding protein 1 (STXBP1) mutations in Chinese patients with early onset epileptic encephalopathy (EOEE) of unknown etiology. METHODS: Targeted next-generation sequencing was used to identify STXBP1 mutations in 143 Chinese patients with EOEE of unknown etiology. A filtering process was applied to prioritize rare variants of potential functional significance. Then Sanger sequencing was employed to validate the parental origin of the variants...
June 13, 2018: Genes, Brain, and Behavior
Melissa T Manners, Nicole L Yohn, Nicholas F Lahens, Gregory R Grant, Marisa S Bartolomei, Julie A Blendy
Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long-term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala - a critical region in the control of emotional states - in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for two-weeks during adolescence and were used to produce two generations of offspring...
June 13, 2018: Genes, Brain, and Behavior
Alexei Morozov, Wataru Ito
Social behaviors largely constitute mutual exchanges of social cues and the responses to them. The adaptive response also requires proper interpretation of the current context. In fear behaviors, social signals have bi-directional effects - some cues elicit or enhance fear whereas other suppress or buffer it. Studies on the social facilitation and social buffering of fear provide evidence of competition between social cues of opposing meanings. Co-expression of opposing cues by the same animal may explain the contradicting outcomes from the interaction between naive and frightened conspecifics, which reflect the fine balance between fear facilitation and buffering...
June 13, 2018: Genes, Brain, and Behavior
Ya-Ting Chang, Chi-Wei Huang, Shu-Hua Huang, Shih-Wei Hsu, Wen-Neng Chang, Jun-Jun Lee, Chiung-Chih Chang
Metabolic connectivity as revealed by [18F] fluorodeoxyglucose positron emission tomography reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical-pathological relationships in patients with Alzheimer's disease. We separately investigated the modulation of two default mode subnetworks, as identified with independent component analysis, by comparing APOE-ε4 carriers to non-carriers with Alzheimer's disease...
June 8, 2018: Genes, Brain, and Behavior
A Merchán, S Mora, B Gago, E Rodriguez-Ortega, A Fernández-Teruel, J L Puga, F Sánchez-Santed, M Moreno, P Flores
Schedule-induced polydipsia (SIP) is an animal model of compulsive drinking that selects for individual differences and varies across rat strains. The aim of this study was to investigate excessive habit formation by analyzing the SIP licking microstructure among rat strains, and to compare the brain areas activated by SIP in different populations. Wistar, Long Evans and Roman High- and Low-Avoidance rat strains were compared using a cluster analysis of 2 main variables, that is, frequency of licking (percentage of interpellet intervals with drinking episodes) and intensity of licking (mean number of licks per interpellet interval), and were found to exhibit high intensity and frequent licking (compulsive drinkers, CD), low intensity but frequent licking (habitual drinkers, HD), and low intensity and low-frequency licking (low drinkers, LD)...
June 7, 2018: Genes, Brain, and Behavior
W Song, L Zhao, Y Tao, X Guo, J Jia, L He, Y Huang, Y Zhu, P Chen, H Qin
Nociceptive stimulus involuntarily interrupts concurrent activities. This interruptive effect is related to the protective function of nociception that is believed to be under stringent evolutionary pressure. To determine whether such interruptive effect is conserved in invertebrate and potentially uncover underlying neural circuits, we examined Drosophila melanogaster. Electric shock (ES) is a commonly used nociceptive stimulus for nociception related research in Drosophila. Here, we showed that background noxious ES dramatically interrupted odor response behaviors in a T-maze, which is termed blocking odor response by electric shock (BOBE)...
May 28, 2018: Genes, Brain, and Behavior
Ryan K Shultzaberger, Sarah J Johnson, Jenee Wagner, Kim Ha, Therese A Markow, Ralph J Greenspan
While social experience has been shown to significantly alter behaviors in a wide range of species, comparative studies that uniformly measure the impact of a single experience across multiple species have been lacking, limiting our understanding of how plastic traits evolve. To address this, we quantified variations in social feeding behaviors across 10 species of Drosophilids, tested the effect of altering rearing context on these behaviors (reared in groups or in isolation), and correlated observed behavioral shifts to accompanying transcriptional changes in the heads of these flies...
May 24, 2018: Genes, Brain, and Behavior
P Adhikari, D Orozco, H Randhawa, F W Wolf
Drug naïve animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors...
May 3, 2018: Genes, Brain, and Behavior
B E Dong, Y Xue, K Sakata
Enriched environment treatment (EET) is a potential intervention for depression by inducing brain-derived neurotrophic factor (BDNF). However, its age dependency remains unclear. We recently found that EET during early-life development (ED) was effective in increasing exploratory activity and anti-despair behavior, particularly in promoter IV-driven BDNF deficient mice (KIV), with the largest BDNF protein induction in the hippocampus and frontal cortex. Here, we further determined age dependency of EET effects on anhedonia and promoter-specific BDNF transcription, by using the sucrose preference test and qRT-PCR...
May 2, 2018: Genes, Brain, and Behavior
C W Bird, B C Baculis, J J Mayfield, G J Chavez, T Ontiveros, D J Paine, A J Marks, A L Gonzales, D Ron, C F Valenzuela
Prenatal exposure to alcohol causes a wide range of deficits known as fetal alcohol spectrum disorders (FASDs). Many factors determine vulnerability to developmental alcohol exposure including timing and pattern of exposure, nutrition and genetics. Here, we characterized how a prevalent single nucleotide polymorphism in the human brain-derived neurotrophic factor (BDNF) gene (val66met) modulates FASDs severity. This polymorphism disrupts BDNF's intracellular trafficking and activity-dependent secretion, and has been linked to increased incidence of neuropsychiatric disorders such as depression and anxiety...
April 24, 2018: Genes, Brain, and Behavior
S van Rijn, L de Sonneville, H Swaab
About 1 in 650 boys are born with an extra X chromosome (47,XXY or Klinefelter syndrome). 47,XXY is associated with vulnerabilities in socio-emotional development. This study was designed to assess types of cognitive deficits in individuals with 47,XXY that may contribute to social-emotional dysfunction, and to evaluate the nature of such deficits at various levels: ranging from basic visuospatial processing deficits, impairments in face recognition (FR), to emotion expression impairments. A total of 70 boys and men with 47,XXY, aged 8 to 60 years old, participated in the study...
July 2018: Genes, Brain, and Behavior
Z Harda, J M Dzik, M Nalberczak-Skóra, K Meyza, K Łukasiewicz, S Łęski, K Radwanska
The α-Ca2+ /calmodulin-dependent protein kinase II (αCaMKII), a key regulator of the glutamatergic synapse, has been implicated in many psychiatric disorders characterized by social impairments. Here we tested whether autophosphorylation of αCaMKII at threonine 286, which prolongs the activity of the enzyme, affects social behaviors in mice. We observed that autophosphorylation-deficient (αCaMKII-T286A) mutant female mice showed abnormal social behaviors characterized by decreased social preference and interest in conspecifics of the same sex, as compared to their wild-type littermates...
June 2018: Genes, Brain, and Behavior
C Ruland, J Berlandi, K Eikmeier, T Weinert, F J Lin, O Ambree, J Seggewiss, W Paulus, A Jeibmann
Environmental factors, such as housing conditions and cognitively stimulating activities, have been shown to affect behavioral phenotypes and to modulate neurodegenerative conditions such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder affecting cognitive functions. Epidemiological evidence and experimental studies using rodent models have indicated that social interaction reduces development and progression of disease. Drosophila models of Aβ42-associated AD lead to AD-like phenotypes, such as long-term memory impairment, locomotor and survival deficits, while effects of environmental conditions on AD-associated phenotypes have not been assessed in the fly...
June 2018: Genes, Brain, and Behavior
K Heslin, L Coutellier
Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia have an expansive array of reported genetic and environmental contributing factors. However, none of these factors alone can account for a substantial proportion of cases of either disorder. Instead, many gene-by-environment interactions are responsible for neurodevelopmental disturbances that lead to these disorders. The current experiment used heterozygous knock-out mice to examine a potential interaction between 2 factors commonly linked to neurodevelopmental disorders and cognitive deficit: imbalanced excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure...
June 2018: Genes, Brain, and Behavior
E H Chang, K Fernando, L W E Yeung, K Barbari, T-S S Chandon, A K Malhotra
The dystrobrevin-binding protein 1 (DTNBP1) gene is a candidate risk factor for schizophrenia and has been associated with cognitive ability in both patient populations and healthy controls. DTNBP1 encodes dysbindin protein, which is localized to synaptic sites and is reduced in the prefrontal cortex and hippocampus of patients with schizophrenia, indicating a potential role in schizophrenia etiology. Most studies of dysbindin function have focused on the sandy (sdy) mice that lack dysbindin protein and have a wide range of abnormalities...
June 2018: Genes, Brain, and Behavior
A L Ujjainwala, C D Courtney, S G Rhoads, J S Rhodes, C A Christian
Neuropsychiatric disorders in which reduced social interest is a common symptom, such as autism, depression, and anxiety, are frequently associated with genetic mutations affecting γ-aminobutyric acid (GABA)ergic transmission. Benzodiazepine treatment, acting via GABA type-A receptors, improves social interaction in male mouse models with autism-like features. The protein diazepam binding inhibitor (DBI) can act as an endogenous benzodiazepine, but a role for DBI in social behavior has not been described. Here, we investigated the role of DBI in the social interest and recognition behavior of mice...
June 2018: Genes, Brain, and Behavior
H Sugimoto, K Ikeda, K Kawakami
Atp1a3 is the Na-pump alpha3 subunit gene expressed mainly in neurons of the brain. Atp1a3-deficient heterozygous mice (Atp1a3+/- ) show altered neurotransmission and deficits of motor function after stress loading. To understand the function of Atp1a3 in a social hierarchy, we evaluated social behaviors (social interaction, aggression, social approach and social dominance) of Atp1a3+/- and compared the rank and hierarchy structure between Atp1a3+/- and wild-type mice within a housing cage using the round-robin tube test and barbering observations...
June 2018: Genes, Brain, and Behavior
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