Rat Genomics Applied to Psychiatric Research

Moisan, Marie‐Pierre; Ramos, André

doi:10.1007/978-1-60327-389-3_25

Cited by 6 publications

(3 citation statements)

References 87 publications

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“…In this sense, the overlap between these behaviors will depend on the genetic background of each population studied and are expected to be mostly partial only (see below). For detailed review of genes related to animal models of anxiety see [55][56][57].…”

Section: The Linkage Of Emotional Traitsmentioning

confidence: 99%

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Gomes

Hassan

Maisonnette

et al. 2013

Behavioural Brain Research

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evaluation of eight rat lines selected for high and low anxiety-related responses" (2013 • Genetic models are powerful tools to help understand anxiety disorders.• In order to determine the extent to which multiple anxiety traits generalize we compared eight genetic lines of rats selected for single high or low emotional responses.• We find many behavioral traits generalize across different animal lines selected for a single trait. a b s t r a c t Anxiety traits can be stable and permanent characteristics of an individual across time that is less susceptible of influences by a particular situation. One way to study trait anxiety in an experimental context is through the use of rat lines, selected according to contrasting phenotypes of fear and anxiety. It is not clear whether the behavioral differences between two contrasting rat lines in one given anxiety test are also present in others paradigms of state anxiety. Here, we examine the extent to which multiple anxiety traits generalize across selected animal lines originally selected for a single anxiety trait. We review the behavioral results available in the literature of eight rat genetic models of trait anxiety -namely Maudsley Reactive and Non-reactive rats, Floripa H and L rats, Tsukuba High and Low Emotional rats, High and Low Anxiety-related rats, High and Low Ultrasonic Vocalization rats, Roman High and Low Avoidance rats, Syracuse High and Low Avoidance rats, and Carioca High and Low Conditioned Freezing rats -across 11 behavioral paradigms of innate anxiety or aversive learning frequently used in the experimental setting. We observed both convergence and divergence of behavioral responses in these selected lines across the 11 paradigms. We find that predisposition for specific anxiety traits will usually be generalized to other anxiety provoking stimuli. However this generalization is not observed across all genetic models indicating some unique trait and state interactions. Genetic models of enhanced-anxiety related responses are beginning to help define how anxiety can manifest differently depending on the underlying traits and the current environmentally induced state. a r t i c l e i n f o

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Section: The Linkage Of Emotional Traitsmentioning

confidence: 99%

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Gomes

Hassan

Maisonnette

et al. 2013

Behavioural Brain Research

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“…Regarding psychiatric-relevant phenotypes, Moisan and Ramos have listed over 160 QTLs that had been mapped in rats until 2010, including their names, chromosome positions, strains and statistical significance [ 44 ]. By analyzing currently available data from the RGD, we have identified 167 QTLs for emotionality-related traits, 82 for stress responses, 56 for anxiety and 64 for locomotor activity, some of which overlap with each other [ 12 ].…”

Section: Qtl Studies In Ratsmentioning

confidence: 99%

Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps

Ramos

Granzotto

Kremer

et al. 2023

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Scientists have systematically investigated the hereditary bases of behaviors since the 19th century, moved by either evolutionary questions or clinically-motivated purposes. The pioneer studies on genetic selection of laboratory animals had already indicated, one hundred years ago, the immense complexity of analyzing behaviors that were influenced by a large number of small-effect genes and an incalculable amount of environmental factors. Merging Mendelian, quantitative and molecular approaches in the 1990s made it possible to map specific rodent behaviors to known chromosome regions. From that point on, Quantitative Trait Locus (QTL) analyses coupled with behavioral and molecular techniques, which involved in vivo isolation of relevant blocks of genes, opened new avenues for gene mapping and characterization. This review aims at examining the QTL strategy applied to the behavioral study of emotionality, with a focus on the laboratory rat. We discuss challenges, advances and limitations of the search for Quantitative Trait Genes (QTG) playing a role in the regulation of emotionality. For the past 25 years, we have marched the long journey from emotionality-related behaviors to genes. In this context, our experiences are used to illustrate why and how one should move forward in the molecular understanding of complex psychiatric illnesses. The promises of exploring genetic links between immunological and emotional responses are also discussed. New strategies based on humans, rodents and other animals (such as zebrafish) are also acknowledged, as they are likely to allow substantial progress to be made in the near future.

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“…It has also helped to identify markers of disease and surrogate markers of drug response in chronic inflammation and age-related diseases (2,17,26). Recent studies, including some from our group, have also shown that M. tuberculosis-infected rats develop organized granulomas within the lungs while controlling the infection over time (32).…”

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confidence: 99%

T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis

Foo

Tay

Siew

et al. 2011

Antimicrob Agents Chemother

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Mycobacterium tuberculosis is the causative agent of a pulmonary epidemic that is estimated to infect one-third of the world's population and that has an increased incidence of multidrug resistance. The evaluation of new chemical entities against M. tuberculosis is hampered by the lack of biological tools to help predict efficacy, from early drug development to clinical trials. As the rat is the animal species of choice in the pharmaceutical industry, we have developed a rat model of acute and chronic phases of M. tuberculosis infection for drug efficacy testing. In this model, we have evaluated the impact of tuberculosis drugs on T cell response using the enzyme-linked immunospot assay methodology. Infected rats treated with isoniazid (INH) or rifampin (RIF) responded to therapy, the potency of which was comparable to that seen in the mouse. Peripheral blood mononuclear cells from infected rats produced gamma interferon (IFN-␥) in response to RD-1 antigens, such as the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa culture filtrate protein (CFP-10). A decrease in IFN-␥ spot-forming cells (SFCs) was consistently observed in response to drug treatment. In both the acute-and chronic-phase models, the T cell response was more sensitive to ESAT-6 than to CFP-10. The SFC count in response to ESAT-6 appears to be an indicator of bacterial killing in the rat. Collectively, our data suggest that the ESAT-6 response could be used as a potential surrogate of drug efficacy in the rat and that such a readout could help shorten drug testing during preclinical development.Mycobacterium tuberculosis infection is among the world's leading infectious diseases, causing about 2 million deaths annually. The emergence of multidrug-resistant M. tuberculosis strains along with the increase of HIV coinfected cases worsens the situation (42). In countries with a high incidence of tuberculosis (TB), TB control programs rely on a diagnostic methods and drugs that have been developed decades ago and that are inadequate to effectively control the epidemic. The urgent need to develop new diagnostic tools as well as new therapeutic interventions is hampered by long clinical trials, where markers of infection and drug response are lacking (38).For decades, the tuberculin skin test (TST) has been used to diagnose TB (18). The TST measures cell-mediated immunity in the form of a delayed-type hypersensitivity response to the purified protein derivative (PPD), a crude mixture of antigens shared among M. tuberculosis, Mycobacterium bovis BCG, and several nontuberculous mycobacteria (NTM). As a result, the TST has lower specificity in populations with high BCG coverage and NTM exposure and shows poor sensitivity in immunocompromised individuals (30). The gamma interferon (IFN-␥) enzyme-linked immunospot (ELISpot) assay has emerged as an alternative to the TST. The assay consists of in vitro stimulation of peripheral blood mononuclear cells (PBMCs) using RD-1 antigens, the 6-kDa early secretory antigen target (ESAT-6) and the 10-kDa cul...

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Rat Genomics Applied to Psychiatric Research

Cited by 6 publications

References 87 publications

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Hunting for Genes Underlying Emotionality in the Laboratory Rat: Maps, Tools and Traps

T Cell Monitoring of Chemotherapy in Experimental Rat Tuberculosis

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