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Genes, Brain, and Behavior

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https://www.readbyqxmd.com/read/27906494/alcohol-dependent-molecular-adaptations-of-the-nmda-receptor-system
#1
REVIEW
Nadege Morisot, Dorit Ron
Phenotypes such as motivation to consume alcohol, goal-directed alcohol seeking and habit formation contribute to the mechanisms underlying heavy alcohol use. Learning and memory processes greatly contribute to the establishment and maintenance of these behavioral phenotypes. The N-Methyl-D-Aspartate receptor (NMDAR) is a driving force of synaptic plasticity, a key cellular hallmark of learning and memory. Here, we describe data in rodents and humans linking signaling molecules that center around the NMDARs and behaviors associated with the development and/or maintenance of alcohol abuse...
December 1, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27886459/standardised-experiments-in-mutant-mice-reveal-behavioural-similarity-on-129s5-and-c57bl-6j-backgrounds
#2
Louie N van de Lagemaat, Lianne E Stanford, Charles Pettit, Douglas J Strathdee, Karen E Strathdee, Kathryn A Elsegood, David G Fricker, Mike D R Croning, Noboru H Komiyama, Seth G N Grant
Behavioural analysis of mice carrying engineered mutations is widely used to identify roles of specific genes in components of the mammalian behavioural repertoire. The reproducibility and robustness of phenotypic measures has become a concern that undermines the use of mouse genetic models for translational studies. Contributing factors include low individual study power, non-standardised behavioural testing, failure to address confounds and differences in genetic background of mutant mice. We have examined the importance of these factors using a statistically robust approach applied to behavioural data obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated in a standardised battery of five behavioural assays...
November 25, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27870313/hypothalamic-specific-proopiomelanocortin-deficiency-reduces-alcohol-drinking-in-male-and-female-mice
#3
Yan Zhou, Marcelo Rubinstein, Malcolm J Low, Mary Jeanne Kreek
Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in both humans and rodents. The present study investigated whether hypothalamic proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE-/-), resulting in hypothalamic-specific POMC deficiency, were studied in short-access (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle), intermittent access (IA, 24-hour cycles of alcohol access every other day, alcohol vs...
November 21, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27860248/restructuring-of-basal-ganglia-circuitry-and-associated-behaviors-triggered-by-low-striatal-d2-receptor-expression-implications-for-substance-use-disorders
#4
REVIEW
Lauren Dobbs, Julia C Lemos, Veronica A Alvarez
Dopamine D2 receptors (D2Rs) consistently emerge as a critical substrate for the etiology of some major psychiatric disorders. Indeed, a central theory of substance use disorders (SUDs) postulates that a reduction in D2R levels in the striatum is a determining factor that confers vulnerability to abuse substances. A large number of clinical and preclinical studies strongly support this link between SUDs and D2Rs; however, identifying the mechanism by which low D2Rs facilitate SUDs has been hindered by the complexity of circuit connectivity, the heterogeneity of D2R expression and the multifaceted constellation of phenotypes observed in SUD patient...
November 17, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27860243/lessons-from-the-canine-oxtr-gene-populations-variants-and-functional-aspects
#5
Melinda Bence, Peter Marx, Eszter Szantai, Eniko Kubinyi, Zsolt Ronai, Zsofia Banlaki
Oxytocin receptor (OXTR) acts as a key behavioral modulator of the central nervous system, affecting social behavior, stress, affiliation and cognitive functions. Variants of the Oxtr gene are known to influence behavior both in animals and humans, however, canine Oxtr polymorphisms are less characterized in terms of possible relevance to function, selection criteria in breeding and domestication. In this report, we provide a detailed characterization of common variants of the canine Oxtr gene. In particular, (1) novel polymorphisms were identified by direct sequencing of wolf and dog samples, (2) allelic distributions and pairwise linkage disequilibrium patterns of several canine populations were compared, (3) neighbor joining tree based on common SNPs was constructed, (4) mRNA expression features were assessed, (5) a novel splice variant was detected and (6) in vitro functional assays were performed...
November 11, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27862969/mediation-of-oxidative-stress-in-hypothalamic-ghrelin-associated-appetite-control-in-rats-treated-with-phenylpropanolamine
#6
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase (SOD), catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT), and the ghrelin receptor (GHSR1a) were examined and compared...
November 8, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27790850/regulation-of-behaviour-by-the-nuclear-receptor-tlx
#7
REVIEW
James D O'Leary, Olivia F O'Leary, John F Cryan, Yvonne M Nolan
The orphan nuclear receptor Tlx (Nr2e1) is a key regulator of both embryonic and adult hippocampal neurogenesis. Several different mouse models have been developed which target Tlx in vivo including spontaneous deletion models (from birth) and targeted and conditional knockouts. Although some conflicting findings have been reported, for the most part studies have demonstrated that Tlx is important in regulating the processes that underlie neurogenesis, spatial learning, anxiety-like behaviour and interestingly, aggression...
October 27, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27790829/the-impact-of-cacna1c-gene-and-its-epistasis-with-znf804a-on-white-matter-microstructure-in-health-schizophrenia-and-bipolar-disorder
#8
Emma-Jane Mallas, Francesco Carletti, Christopher A Chaddock, Sukhi Shergill, James Woolley, Marco M Picchioni, Colm McDonald, Timothea Toulopoulou, Eugenia Kravariti, Sridevi Kalidindi, Elvira Bramon, Robin Murray, Gareth J Barker, Diana P Prata
Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the zinc-finger ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health...
October 27, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27762100/inhibition-of-dna-methyltransferases-regulates-cocaine-self-administration-by-rats-a-genome-wide-dna-methylation-study
#9
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
https://www.readbyqxmd.com/read/27762084/variants-in-the-cnr1-gene-predispose-to-headache-with-nausea-in-the-presence-of-life-stress
#10
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
https://www.readbyqxmd.com/read/27762066/a-new-brain-dopamine-deficient-drosophila-and-its-pharmacological-and-genetic-rescue
#11
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
https://www.readbyqxmd.com/read/27749013/high-motivation-for-exercise-is-associated-with-altered-chromatin-regulators-of-monoamine-receptor-gene-expression-in-the-striatum-of-selectively-bred-mice
#12
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
https://www.readbyqxmd.com/read/27749004/neurobiology-of-co-morbid-post-traumatic-stress-disorder-alcohol-use-disorder
#13
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
https://www.readbyqxmd.com/read/27736018/cognition-in-aged-rhesus-monkeys-effect-of-dhea-and-correlation-with-steroidogenic-gene-expression
#14
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 touch screen 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
https://www.readbyqxmd.com/read/27706932/do-specific-nmda-receptor-subunits-act-as-gateways-for-addictive-behaviors
#15
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
https://www.readbyqxmd.com/read/27706910/sweetened-ethanol-drinking-during-social-isolation-enhanced-intake-resistance-to-genetic-heterogeneity-and-the-emergence-of-a-distinctive-drinking-pattern-in-adolescent-mice
#16
J B Panksepp, E D Rodriguez, A 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, PD, 21), and then given continuous access to two fluids on PDs 34-45: one containing water and the other containing an ascending series of saccharin-sweetened ethanol (3-6-10%)...
October 5, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27717169/5ht2a-receptor-blockade-in-dorsomedial-striatum-reduces-repetitive-behaviors-in-btbr-mice
#17
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
https://www.readbyqxmd.com/read/27657733/reprogramming-of-mpfc-transcriptome-and-function-in-alcohol-dependence
#18
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
https://www.readbyqxmd.com/read/27648526/the-influence-of-fkbp5-genotype-on-expression-of-fkbp5-and-other-glucocorticoid-regulated-genes-dependent-on-trauma-exposure
#19
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
https://www.readbyqxmd.com/read/27643807/muscle-spindle-alterations-precede-onset-of-sensorimotor-deficits-in-charcot-marie-tooth-type-2e
#20
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
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