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Genes, Brain, and Behavior

Mathieu Fonteneau, Dominique Filliol, Patrick Anglard, Katia Befort, Pascal Romieu, Jean Zwiller
DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine and zebularine actually enhanced the reinforcing properties of cocaine. To get some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated or not with 5-aza-2'-deoxycytidine...
October 20, 2016: Genes, Brain, and Behavior
Gabriella Juhasz, Eva Csepany, Mate Magyar, Andrea Edit Edes, Nora Eszlari, Gabor Hullam, Peter Antal, Gyongyi Kokonyei, Ian Muir Anderson, John Francis William Deakin, Gyorgy Bagdy
One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 (CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population (n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events (RLE), and covered the CNR1 gene with 11 SNPs...
October 19, 2016: Genes, Brain, and Behavior
Karol Cichewicz, Emma J Garren, Chika Adiele, Yoshinori Aso, Zhang Wang, Martin Wu, Serge Birman, Gerald M Rubin, Jay Hirsh
Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA deficient flies were previously generated using tissue selective GAL4-UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH...
October 19, 2016: Genes, Brain, and Behavior
Michael Saul, Petra Majdak, Samuel Perez, Matthew Reilly, Theodore Garland, Justin S Rhodes
Though exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days...
October 17, 2016: Genes, Brain, and Behavior
Nicholas W Gilpin, Jeff L Weiner
Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly co-morbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of co-morbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on co-morbid PTSD and AUD: we summarize epidemiological data documenting the prevalence of this co-morbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD, and discuss successes and failures of past and current treatment strategies...
October 17, 2016: Genes, Brain, and Behavior
K G Sorwell, L Renner, A R Weiss, M Neuringer, S G Kohama, H F Urbanski
Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved in perimenopausal animals using alternative hormonal supplements we administered dehydroepiandrosterone (DHEA) to old ovary-intact female rhesus macaques for ~2.5 months. Using computerized touchscreen memory tasks, including delayed response (DR) and delayed matching-to-sample (DMS), we observed improved performance with time in all of the animals but failed to detect a significant effect of DHEA...
October 13, 2016: Genes, Brain, and Behavior
F Woodward Hopf
Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory...
October 5, 2016: Genes, Brain, and Behavior
Jules B Panksepp, Eduardo D Rodriguez, Andrey E Ryabinin
With its ease of availability during adolescence, sweetened ethanol ('alcopops') is consumed within many contexts. We asked here whether genetically based differences in social motivation are associated with how the adolescent social environment impacts voluntary ethanol intake. Mice with previously described differences in sociability (BALB/cJ, C57BL/6J, FVB/NJ and MSM/MsJ strains) were weaned into isolation or same-sex pairs (postnatal day 21), and then given continuous access to two fluids on postnatal days 34-45: One containing water and the other containing a ascending series of saccharin-sweetened ethanol (3-to-6-to-10%)...
October 5, 2016: Genes, Brain, and Behavior
Todd D Gould
No abstract text is available yet for this article.
September 28, 2016: Genes, Brain, and Behavior
D A Amodeo, E Rivera, E H Cook, J A Sweeney, M E Ragozzino
Restricted and repetitive behaviors are a defining feature of autism, which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT2A receptor activity is altered in autism, while recent work indicates that systemic 5HT2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT2A receptors are expressed in the orbitofrontal cortex and striatum...
September 22, 2016: Genes, Brain, and Behavior
Markus Heilig, Estelle Barbier, Andrea Lynn Johnstone, Jenica Tapocik, Marcus W Meinhardt, Simone Pfarr, Claes R Wahlestedt, Wolfgang H Sommer
Despite its limited immediate reinforcement value, alcohol has a potent ability to induce neuroadaptations that promote its incentive salience, escalation of voluntary alcohol intake and aversion resistant alcohol seeking. A constellation of these traits, collectively called "post-dependent", emerges following brain exposure to repeated cycles of intoxication and withdrawal. The medial prefrontal cortex (mPFC) and its subdivisions exert top-down regulation of approach and avoidance behaviors, including those that lead to alcohol intake...
September 22, 2016: Genes, Brain, and Behavior
S Yeo, M-A Enoch, E Gorodetsky, L Akhtar, K Schuebel, A Roy, D Goldman
The FK506 binding protein 51 (FKBP5), an intrinsic regulator of the glucocorticoid receptor, has been associated with pathological behaviors particularly in the context of childhood trauma (CT), via a putatively regulatory polymorphism, rs1360780. However, trans- and cis-acting effects of this locus and its interaction with CT are incompletely understood. To study its effects on the expression of glucocorticoid-regulated genes including FKBP5, we used lymphoblastoid cell lines (LCLs) derived from 16 CT-exposed patients with greater than two substance dependence/suicidal behavior diagnoses (casesCT+) and 13 non-CT-exposed controls (controlsCT-)...
September 20, 2016: Genes, Brain, and Behavior
E Villalón, M R Jones, C Sibigtroth, S J Zino, J M Dale, D S Landayan, H Shen, D D W Cornelison, M L Garcia
Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-L(E396K) ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-L(E396K) mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered...
September 19, 2016: Genes, Brain, and Behavior
T L Wise
Fragile X syndrome (FXS) is an inherited form of intellectual disability that is usually caused by expansion of a polymorphic CGG repeat in the 5' untranslated region of the X-linked FMR1 gene, which leads to hypermethylation and transcriptional silencing. Two non-neurological phenotypes of FXS are enlarged testes and connective tissue dysplasia, which could be caused by alterations in a growth factor signaling pathway. FXS patients also frequently have autistic-like symptoms, suggesting that the signaling pathways affected in FXS may overlap with those affected in autism...
September 19, 2016: Genes, Brain, and Behavior
B Wang, Y Zheng, H Shi, X Du, Y Zhang, B Wei, M Luo, H Wang, X Wu, X Hua, M Sun, X Xu
Zfp462 is a newly identified vertebrate-specific zinc finger protein that contains nearly 2500 amino acids and 23 putative C2H2-type zinc finger domains. So far, the functions of Zfp462 remain unclear. In our study, we showed that Zfp462 is expressed predominantly in the developing brain, especially in the cerebral cortex and hippocampus regions from embryonic day 7.5 to early postnatal stage. By using a piggyBac transposon-generated Zfp462 knockout (KO) mouse model, we found that Zfp462 KO mice exhibited prenatal lethality with normal neural tube patterning, whereas heterozygous (Het) Zfp462 KO (Zfp462(+/-) ) mice showed developmental delay with low body weight and brain weight...
September 13, 2016: Genes, Brain, and Behavior
K M Holleran, D G Winder
Negative reinforcement is widely thought to play an important role in chronic alcohol-use disorders (AUDs), and high comorbidity between AUDs and affective disorders highlights the importance of investigating this relationship. Prominent models posit that repeated cycles of alcohol (ethanol, EtOH) exposure and withdrawal produce circuit adaptations in the central nervous system that drive a transition from positive- to negative reinforcement-based alcohol seeking. Evidence supporting this theory has accumulated in large part using forced EtOH administration models, such as chronic intragastric gavage and chronic vapor inhalation...
September 13, 2016: Genes, Brain, and Behavior
K Tombeau Cost, E Unternaehrer, A Plamondon, M Steiner, M Meaney, L Atkinson, J L Kennedy, A S Fleming
Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post-partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada...
September 13, 2016: Genes, Brain, and Behavior
S Y-S Khoo, G D Gibson, A A Prasad, G P McNally
The contexts where drugs are self-administered play an important role in regulating persistent drug taking and in relapse to such taking after periods of abstinence. Here, we review the behavioral and brain mechanisms enabling contexts to promote and prevent relapse to drug seeking. We review the key brain structures, their neuropharmacology and their connectivity. We discuss the similarities and differences between the mechanisms for context-induced reinstatement of drug seeking vs. other forms of relapse to drug seeking in animal models and we highlight the numerous deficits in our understanding...
September 10, 2016: Genes, Brain, and Behavior
Rolf W Stottmann, Ashley Driver, Arnold Gutierrez, Matthew R Skelton, Michael Muntifering, Christopher Stepien, Luke Knudson, Matthew Kofron, Charles V Vorhees, Michael T Williams
Development of the mammalian forebrain requires a significant contribution from tubulin proteins to physically facilitate both the large number of mitoses in the neurogenic brain (in the form of mitotic spindles) as well as support cellular scaffolds to guide radial migration (radial glial neuroblasts). Recent studies have identified a number of mutations in human tubulin genes affecting the forebrain, including TUBB2B . We previously identified a mouse mutation in Tubb2b and we show here that mice heterozygous for this missense mutation in Tubb2b have significant cognitive defects in spatial learning and memory...
September 4, 2016: Genes, Brain, and Behavior
E M Leerkes, J Su, S Calkins, V C Henrich, A Smolen
We examined the extent to which the arginine vasopressin receptor 1a (AVPR1a) and dopamine receptor D4 (DRD4) were related to sensitive maternal behavior directly or indirectly via maternal social cognition. Participants were 207 (105 European-American and 102 African-American) mothers and their children (52% females). Sensitive maternal behavior was rated and aggregated across a series of tasks when infants were 6 months, 1 year and 2 years old. At 6 months, mothers were interviewed about their empathy, attributions about infant behavior and beliefs about crying to assess their parenting-related social cognition...
September 1, 2016: Genes, Brain, and Behavior
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