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Genes, Brain, and Behavior

Pratik Adhikari, Donnoban Orozco, Harpreet Randhawa, Fred 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
Brittany E Dong, Yueqiang Xue, Kazuko 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
Clark W Bird, Brian C Baculis, Jacob J Mayfield, Glenna J Chavez, Tiahna Ontiveros, Dana J Paine, Aaron J Marks, Alicia L Gonzales, Dorit Ron, C Fernando 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
Sonali N Reisinger, Eryan Kong, Barbara Molz, Thomas Humberg, Spyros Sideromenos, Ana Cicvaric, Thomas Steinkellner, Jae-Won Yang, Maureen Cabatic, Francisco J Monje, Harald H Sitte, Benjamin J Nichols, Daniela D Pollak
Aberrant serotonergic neurotransmission in the brain is considered at the core of the pathophysiological mechanisms involved in neuropsychiatric disorders. Gene by environment interactions contribute to the development of depression and involve modulation of the availability and functional activity of the serotonin transporter (SERT). Using behavioral and in vivo electrophysiological approaches together with biochemical, molecular-biological and molecular imaging tools we establish Flotillin-1 (Flot1) as a novel protein interacting with SERT and demonstrate its involvement in the response to chronic corticosterone (CORT) treatment...
April 18, 2018: Genes, Brain, and Behavior
M Manca, V Pessoa, P Myers, A Pickles, J Hill, H Sharp, C Murgatroyd, V J Bubb, J P Quinn
Monoamine oxidase-A (MAOA) metabolises monoamines and is implicated in the pathophysiology of psychiatric disorders. A polymorphic repetitive DNA domain, termed the uVNTR (upstream variable number tandem repeat), located at the promoter of the MAOA gene is a risk factor for many of these disorders. MAOA is on the X chromosome suggesting gender could play a role in regulation. We analysed MAOA regulation in the human female cell line, SH-SY5Y, which is polymorphic for the uVNTR. This heterozygosity allowed us to correlate allele specific gene expression with allele specific transcription factor binding and epigenetic marks for MAOA...
April 18, 2018: Genes, Brain, and Behavior
Chisato Shimanoe, Tsuyoshi Hachiya, Megumi Hara, Yuichiro Nishida, Keitaro Tanaka, Yoichi Sutoh, Atsushi Shimizu, Asahi Hishida, Sayo Kawai, Rieko Okada, Takashi Tamura, Keitaro Matsuo, Hidemi Ito, Etsuko Ozaki, Daisuke Matsui, Rie Ibusuki, Ippei Shimoshikiryo, Naoyuki Takashima, Aya Kadota, Kokichi Arisawa, Hirokazu Uemura, Sadao Suzuki, Miki Watanabe, Kiyonori Kuriki, Kaori Endoh, Haruo Mikami, Yohko Nakamura, Yukihide Momozawa, Michiaki Kubo, Masahiro Nakatochi, Mariko Naito, Kenji Wakai
Individuals use coping behaviors to deal with unpleasant daily events. Such behaviors can moderate or mediate the pathway between psychosocial stress and health-related outcomes. However, few studies have examined the associations between coping behaviors and genetic variants. We conducted a genome-wide association study (GWAS) on coping behaviors in 13,088 participants aged 35-69 years as part of the Japan Multi-Institutional Collaborative Cohort Study. Five coping behaviors (emotional expression, emotional support seeking, positive reappraisal, problem solving, and disengagement) were measured and analyzed...
April 17, 2018: Genes, Brain, and Behavior
Andrew J Schork, Timothy T Brown, Donald J Hagler, Wesley K Thompson, Chi-Hua Chen, Anders M Dale, Terry L Jernigan, Natacha Akshoomoff
Executive functions are a diverse and critical suite of cognitive abilities that are often disrupted in individuals with psychiatric disorders. Despite their moderate to high heritability, little is known about the molecular genetic factors that contribute to variability in executive function and how these factors may be related to those that predispose to psychiatric illness. We examined the relationship between polygenic risk scores built from large genome-wide association studies of psychiatric illness and executive functioning in typically developing children...
April 16, 2018: Genes, Brain, and Behavior
Pei-Tan Hsueh, Hsi-Hsun Lin, Hsuan-Han Wang, Chiu-Lin Liu, Wei-Fen Ni, Jong-Kang Liu, Hsin-Hou Chang, Der-Shan Sun, Yao-Shen Chen, Ya-Lei Chen
The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that up-regulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring...
April 15, 2018: Genes, Brain, and Behavior
Bolati Wulaer, Taku Nagai, Akira Sobue, Norimichi Itoh, Keisuke Kuroda, Kozo Kaibuchi, Toshitaka Nabeshima, Kiyofumi Yamada
Disrupted-in-schizophrenia 1 (Disc1) is a key molecular driver for the biology of mental diseases. In order to investigate its role in brain function, we previously generated mice lacking exons 2 and 3 of Disc1 on a C57BL/6J genetic background (Disc1Δ2-3/Δ2-3 mice), which have a deficiency of the full-length Disc1 protein. In the present study, we examined the role of Disc1 in cognitive function using a touchscreen-based visual discrimination task in which mice had to discriminate one of two stimuli simultaneously displayed on the screen and received a liquid reward...
April 10, 2018: Genes, Brain, and Behavior
Karine Yu Sarkisova, Alla V Gabova
WAG/Rij rats, a genetic animal model of absence epilepsy with comorbidity of depression, exhibit behavioral depression-like symptoms and spontaneous generalized spike-wave discharges (SWDs) in the EEG at the age of 6-8 months. The aim of the present study was to test the hypothesis that maternal care is an environmental factor which, along with genetic predisposition, may contribute to the expression of absence seizures and depression-like comorbidity later in life. To achieve this, a cross-fostering procedure was used...
March 31, 2018: Genes, Brain, and Behavior
Elisha M Wachman, Marie J Hayes, Hira Shrestha, Fnu Nikita, Angela Nolin, Leonie Hoyo, Katrina Daigle, Hendrée E Jones, David A Nielsen
Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ-opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother-infant dyads is associated with differences in NAS severity in an independent cohort. Full-term opioid-exposed newborns and their mothers (N=68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing...
March 25, 2018: Genes, Brain, and Behavior
Gregoire Maroteaux, Tanzil Mahmud Arefin, Laura-Adela Harsan, Emmanuel Darcq, Sami Ben Hamida, Brigitte Lina Kieffer
Mouse models are widely used to understand genetic bases of behavior. Traditional testing typically requires multiple experimental settings, captures only snapshots of behavior, and involves human intervention. The recent development of automated home cage monitoring offers an alternative method to study mouse behavior in their familiar and social environment, and over weeks. Here we used the IntelliCage system to test this approach for mouse phenotyping, and studied mice lacking the Gpr88 that have been extensively studied using standard testing...
March 25, 2018: Genes, Brain, and Behavior
Heidi C O'Neill, Charles R Wageman, Sarah E Sherman, Sharon R Grady, Michael J Marks, Jerry A Stitzel
A single nucleotide polymorphism (SNP) in CHRNA5 (rs16969968, change from an aspartic acid (D) to asparagine (N) at position 398 of the human α5 nicotinic acetylcholine receptor subunit) has been associated with increased risk for nicotine dependence. Consequently, carriers of the risk variant may be at elevated risk for in utero nicotine exposure. To assess whether this gene-environment interaction might impact nicotine intake in developmental nicotine-exposed offspring, we utilized a mouse expressing this human SNP...
March 24, 2018: Genes, Brain, and Behavior
A Abdellaoui, M G Nivard, J-J Hottenga, I Fedko, K J H Verweij, B M L Baselmans, E A Ehli, G E Davies, M Bartels, D I Boomsma, J T Cacioppo
Loneliness is a heritable trait that accompanies multiple disorders. The association between loneliness and mental health indices may partly be due to inherited biological factors. We constructed polygenic scores for 27 traits related to behavior, cognition and mental health and tested their prediction for self-reported loneliness in a population-based sample of 8798 Dutch individuals. Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar disorder were significantly associated with loneliness...
March 23, 2018: Genes, Brain, and Behavior
Flurin Cathomas, Damiano Azzinnari, Giorgio Bergamini, Hannes Sigrist, Michaela Buerge, Vanessa Hoop, Benedikt Wicki, Lea Goetze, Sergio Soares, Diana Kukelova, Erich Seifritz, Sandra Goebbels, Klaus-Armin Nave, M Said Ghandour, Cathal Seoighe, Tobias Hildebrandt, German Leparc, Holger Klein, Elia Stupka, Bastian Hengerer, Christopher R Pryce
Oligodendrocyte gene expression is down-regulated in stress-related neuropsychiatric disorders, including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes in brain and emotional behavior, and the present study demonstrates the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing was conducted with prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of affected genes, and cell deconvolution was applied...
March 22, 2018: Genes, Brain, and Behavior
Yonwoo Jung, David Goldman
Much progress in our understanding of RNA metabolism has been made since the first RNA nucleoside modification was identified in 1957. Many of these modifications are found in non-coding RNAs but recent interest has focused on coding RNAs. Here we summarize current knowledge of cellular consequences of RNA modifications, with a special emphasis on neuropsychiatric disorders. We present evidence for the existence of an "RNA code", similar to the histone code, that fine-tunes gene expression in the nervous system by using combinations of different RNA modifications...
March 15, 2018: Genes, Brain, and Behavior
C Molnar, B Estrada, J F de Celis
Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells...
March 9, 2018: Genes, Brain, and Behavior
A Adinolfi, C Carbone, D Leo, R R Gainetdinov, G Laviola, W Adriani
Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder characterized by a developmentally inappropriate, pervasive and persistent pattern of severe inattention, hyperactivity and impulsivity. Despite onset in early childhood, ADHD may continue into adulthood with substantial impairment in social, academic and occupational functioning. A new animal model of this disorder was developed in rats with genetic deletion of the dopamine transporter (DAT) gene (dopamine transporter knockout rats; DAT-KO rats)...
April 2018: Genes, Brain, and Behavior
E C Shontz, C L Souders, J T Schmidt, C J Martyniuk
Dopamine (DA) plays a significant role in cognition, motor function and social behavior. The objectives of this study were to (1) quantify the temporal expression of transcripts (DA receptors, transporters and tyrosine hydroxylase) associated with DA signaling during early stages of zebrafish development and (2) determine their expression profiles following treatment with a D2 receptor antagonist domperidone (DMP). We also assessed locomotor behavior following treatment with DMP using alternating periods of light and dark (ie, dark photokinesis), as DA plays a key role in behavior...
April 2018: Genes, Brain, and Behavior
A Holmes
No abstract text is available yet for this article.
March 2018: Genes, Brain, and Behavior
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