Genes, drugs and behavior: polygenic behavioral phenotypes and single gene manipulations

1999 ◽  
Vol 147 (1) ◽  
pp. 1-1
Author(s):  
Klaus A. Miczek ◽  
S. Barak Caine
Keyword(s):  
Single Gene ◽  
Behavioral Phenotypes ◽  
And Behavior

scholarly journals Functions of Gtf2i and Gtf2ird1 in the developing brain: transcription, DNA-binding, and long term behavioral consequences

2019 ◽  
Author(s):  
Nathan D. Kopp ◽  
Kayla R. Nygaard ◽  
Katherine B. McCullough ◽  
Susan E. Maloney ◽  
Harrison W. Gabel ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Conditioned Fear ◽  
Developing Brain ◽  
Ctcf Binding ◽  
Microdeletion Syndrome ◽  
Behavioral Phenotypes ◽  
Marble Burying ◽  
And Behavior

AbstractGtf2ird1 and Gtf2i may mediate aspects of the cognitive and behavioral phenotypes of Williams Syndrome (WS) – a microdeletion syndrome encompassing these transcription factors (TFs). Knockout mouse models of each TF show behavioral phenotypes. Here we identify their genomic binding sites in the developing brain, and test for additive effects of their mutation on transcription and behavior. Both TFs target constrained chromatin modifier and synaptic protein genes, including a significant number of ASD genes. They bind promoters, strongly overlap CTCF binding and TAD boundaries, and moderately overlap each other, suggesting epistatic effects. We used single and double mutants to test whether mutating both TFs will modify transcriptional and behavioral phenotypes of single Gtf2ird1 mutants. Despite little difference in DNA-binding and transcriptome-wide expression, Gtf2ird1 mutation caused balance, marble burying, and conditioned fear phenotypes. However, mutating Gtf2i in addition to Gtf2ird1 did not further modify transcriptomic or most behavioral phenotypes, suggesting Gtf2ird1 mutation alone is sufficient.

scholarly journals Williams Syndrome As a Model for Elucidation of the Pathway Genes - the Brain - Cognitive Functions: Genetics and Epigenetics

Acta Naturae ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Е. А. Nikitina ◽  
A. V. Medvedeva ◽  
G. А. Zakharov ◽  
Е. V. Savvateeva-Popova
Keyword(s):  
Simple Model ◽  
Williams Syndrome ◽  
Cognitive Functions ◽  
Single Gene ◽  
Model Systems ◽  
Epigenetic Events ◽  
Simple Model System ◽  
And Behavior ◽  
Brain Behavior ◽  
The Brain

Genomic diseases or syndromes with multiple manifestations arise spontaneously and unpredictably as a result of contiguous deletions and duplications generated by unequal recombination in chromosomal regions with a specific architecture. The Williams syndrome is believed to be one of the most attractive models for linking genes, the brain, behavior and cognitive functions. It is a neurogenetic disorder resulting from a 1.5 Mb deletion at 7q11.23 which covers more than 20 genes; the hemizigosity of these genes leads to multiple manifestations, with the behavioral ones comprising three distinct domains: 1) visuo-spatial orientation; 2) verbal and linguistic defect; and 3) hypersocialisation. The shortest observed deletion leads to hemizigosity in only two genes: eln and limk1. Therefore, the first gene is supposed to be responsible for cardiovascular pathology; and the second one, for cognitive pathology. Since cognitive pathology diminishes with a patients age, the original idea of the crucial role of genes straightforwardly determining the brains morphology and behavior was substituted by ideas of the brains plasticity and the necessity of finding epigenetic factors that affect brain development and the functions manifested as behavioral changes. Recently, non-coding microRNAs (miRs) began to be considered as the main players in these epigenetic events. This review tackles the following problems: is it possible to develop relatively simple model systems to analyze the contribution of both a single gene and the consequences of its epigenetic regulation in the formation of the Williams syndromes cognitive phenotype? Is it possible to use Drosophila as a simple model system?

Aplysia Bag Cells Function as a Distributed Neurosecretory Network

2008 ◽  
Vol 99 (1) ◽  
pp. 333-343 ◽  
Author(s):  
Nathan G. Hatcher ◽  
Jonathan V. Sweedler
Keyword(s):  
Single Gene ◽  
Egg Laying ◽  
Site Specific ◽  
Cell Clusters ◽  
Cell Network ◽  
Flight Mass Spectrometry ◽  
Bag Cells ◽  
And Behavior ◽  
Bag Cell Neurons ◽  
Neuroendocrine Systems

The anatomical organization of many neuroendocrine systems implies multiple sites of hormone release in areas mediating multiple aspects of physiology and behavior, yet this neurosecretory complexity has not often been verified. Here we probe the well-characterized hormonal model, the reproductive bag cell neuroendocrine system of the sea slug Aplysia californica. The bag cell neurons of Aplysia mediate egg-laying behavior through the coordinated secretion of a suite of peptides derived from a single gene product, the egg-laying prohormone (proELH). Although the majority of bag cell neurons are located within two major abdominal bag cell clusters, smaller groups of egg-laying hormone-expressing cells have been observed in specific pleural and cerebral ganglia regions, some of which have been reported to be electrically connected to the abdominal bag cell clusters. Releasates are sampled from discrete locations within the Aplysia CNS before and during stimulation of afterdischarge activity and subsequently analyzed with matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Site-specific release profiles are observed at bag cell cluster, pleural, and genital ganglion sites after site-specific electrophysiological activation of bag cell afterdischarges. These data demonstrate that the bag cell network has multiple neurohemal release sites, exhibits descending activation that travels from the cerebral and pleural ganglia down to the abdominal bag cell clusters, and releases spatially distinct profiles of proELH-derived peptides within the Aplysia nervous system. Such distributed neurosecretory organization may be a common feature of neuroendocrine systems across higher order organisms linking multiple behavioral aspects to a single neuronal network.

The behavioral neurogenetics of fragile X syndrome: Analyzing gene–brain–behavior relationships in child developmental psychopathologies

2003 ◽  
Vol 15 (4) ◽  
pp. 927-968 ◽  
Author(s):  
ALLAN L. REISS ◽  
CHRISTOPHER C. DANT
Keyword(s):  
Environmental Factors ◽  
Fragile X Syndrome ◽  
Neurodevelopmental Disorders ◽  
Fragile X ◽  
Single Gene ◽  
Structure And Function ◽  
Research Approach ◽  
And Function ◽  
And Behavior ◽  
Brain Behavior

Analyzing gene–brain–behavior linkages in childhood neurodevelopmental disorders, a research approach called “behavioral neurogenetics,” has provided new insights into understanding how both genetic and environmental factors contribute to complex variations in typical and atypical human development. Research into etiologically more homogeneous disorders, such as fragile X syndrome, in particular, allows the use of more precise metrics of genetic risk so that we can more fully understand the complex pathophysiology of childhood onset neurodevelopmental disorders. In this paper, we review our laboratory's behavioral neurogenetics research by examining gene–brain–behavior relationships in fragile X syndrome, a single-gene disorder that has become a well-characterized model for studying neurodevelopmental dysfunction in childhood. Specifically, we examine genetic influences, trajectories of cognition and behavior, variation in brain structure and function, and biological and environmental factors that influence developmental and cognitive outcomes of children with fragile X. The converging approaches across these multilevel scientific domains indicate that fragile X, which arises from disruption of a single gene leading to the loss of a specific protein, is associated with a cascade of aberrations in neurodevelopment, resulting in a central nervous system that is suboptimal with respect to structure and function. In turn, structural and functional brain alterations lead to early disruption in emotion, cognition, and behavior in the child with fragile X. The combination of molecular genetics, neuroimaging, and behavioral research have advanced our understanding of the linkages between genetic variables, neurobiological measures, IQ, and behavior. Our research and that of others demonstrates that neurobehavior and neurocognition, genetics, and neuroanatomy are all different views of the same intriguing biological puzzle, a puzzle that today is rapidly emerging into a more complete picture of the intricate linkages among gene, brain, and behavior in developing children. Understanding the complex multilevel scientific perspective involved in fragile X will also contribute to our understanding of normal development by highlighting developmental events throughout the life span, thereby helping us to delineate the boundaries of pathology.

scholarly journals Understanding Stress-Related Behavioral Phenotypes: Report from the 1st International Neuroscience Summer School and the 11th International “Stress and Behavior” Conference

2008 ◽  
Vol 2008 ◽  
pp. 1-4
Author(s):  
J. L. LaPorte ◽  
V. M. Klimenko ◽  
A. V. Kalueff
Keyword(s):  
Summer School ◽  
Behavioral Neuroscience ◽  
Social Program ◽  
Medical Doctors ◽  
Behavioral Phenotypes ◽  
Stress Research ◽  
Collaborative Environment ◽  
International Stress ◽  
And Behavior

The 1st International Neuroscience Summer School and the 11th International Multidisciplinary Neuroscience and Biopsychiatry Conference on Stress and Behavior were held in St. Petersburg, Russia, during May 9–20, 2008. The summer school gathered 30 talented young scientists from 15 countries worldwide, and was dedicated to different topics of behavioral neuroscience. Many interactive courses were provided on neuropharmacology, animal phenotyping, and biopsychology. The conference's excellent scientific and social program attracted almost 500 delegates from 40 countries from many areas of stress research. The eclectic interaction between medical doctors, basic scientists, psychologists, and students made for a productive and collaborative environment, which contributed greatly to the success of the school and conference.

scholarly journals The Interaction between Bmal1 and Per2 in Mouse BMSC Osteogenic Differentiation

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Haiya Zhuo ◽  
Yuhong Wang ◽  
Qing Zhao
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Osteogenic Differentiation ◽  
Lentiviral Vector ◽  
Single Gene ◽  
Adenovirus Vector ◽  
Bone Volume ◽  
Volume Changes ◽  
And Behavior ◽  
Gene Inhibition

The circadian clock is a system that controls endogenous time of organisms, and it regulates the physiology and behavior of bodies. The transcription factors Brain and Muscle ARNT-like Protein 1 (BMAL1) and Period2 (Per2) are components of the circadian clock, and they play vital roles in circadian clock function. Both Bmal1−/− mice and Per2−/− mice display obvious bone volume changes. In this study, we inhibited the expression of Bmal1 in bone marrow-derived mesenchymal stem cells (BMSCs) using a lentiviral vector harboring RNAi sequences, which increased the osteogenic differentiation capability of BMSCs. We also suppressed Per2 gene expression using an adenovirus vector harboring RNAi sequences, and similarly, the osteogenic differentiation ability of BMSCs was enhanced. Furthermore, when both Bmal1 and Per2 gene expression was suppressed in BMSCs by lentiviral and adenoviral interference, the osteogenic differentiation capability was stronger than that in BMSCs following single-gene inhibition. Our data support that both Bmal1 and Per2 play negative roles in BMSC osteogenic differentiation and that Bmal1 and Per2 have a synergistic effect on the osteogenic differentiation of BMSCs.

scholarly journals Developmental loss of MeCP2 from VIP interneurons impairs cortical function and behavior

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
James M Mossner ◽  
Renata Batista-Brito ◽  
Rima Pant ◽  
Jessica A Cardin
Keyword(s):  
Rett Syndrome ◽  
Neurodevelopmental Disorder ◽  
Critical Role ◽  
Cell Types ◽  
Loss Of Function ◽  
Cortical Function ◽  
Behavioral Phenotypes ◽  
Pathophysiological Role ◽  
And Function ◽  
And Behavior

Rett Syndrome is a devastating neurodevelopmental disorder resulting from mutations in the gene MECP2. Mutations of Mecp2 that are restricted to GABAergic cell types largely replicate the behavioral phenotypes associated with mouse models of Rett Syndrome, suggesting a pathophysiological role for inhibitory interneurons. Recent work has suggested that vasoactive intestinal peptide-expressing (VIP) interneurons may play a critical role in the proper development and function of cortical circuits, making them a potential key point of vulnerability in neurodevelopmental disorders. However, little is known about the role of VIP interneurons in Rett Syndrome. Here we find that loss of MeCP2 specifically from VIP interneurons replicates key neural and behavioral phenotypes observed following global Mecp2 loss of function.

How Homo economicus lost her mind and how we can revive her

2018 ◽  
Vol 41 ◽  
Author(s):  
Peter DeScioli
Keyword(s):  
Economic Thought ◽  
History Of Economic Thought ◽  
Homo Economicus ◽  
Economic Theories ◽  
Target Article ◽  
History Of ◽  
The Mind ◽  
And Behavior

AbstractThe target article by Boyer & Petersen (B&P) contributes a vital message: that people have folk economic theories that shape their thoughts and behavior in the marketplace. This message is all the more important because, in the history of economic thought, Homo economicus was increasingly stripped of mental capacities. Intuitive theories can help restore the mind of Homo economicus.

The parent-offspring microbiome and neurobehavioral development

2019 ◽  
Vol 42 ◽  
Author(s):  
Jeffrey R. Alberts ◽  
Christopher Harshaw ◽  
Gregory E. Demas ◽  
Cara L. Wellman ◽  
Ardythe L. Morrow
Keyword(s):  
Mammalian Species ◽  
Social Emotional ◽  
Behavioral Measures ◽  
Neurobehavioral Development ◽  
Emotional Function ◽  
Neurobehavioral Outcomes ◽  
Methodological Approaches ◽  
And Behavior

Abstract We identify the significance and typical requirements of developmental analyses of the microbiome-gut-brain (MGB) in parents, offspring, and parent-offspring relations, which have particular importance for neurobehavioral outcomes in mammalian species, including humans. We call for a focus on behavioral measures of social-emotional function. Methodological approaches to interpreting relations between the microbiota and behavior are discussed.

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