Thyroid Hormone Receptors Function in GABAergic Neurons During Development and in Adults.

The nuclear receptors of thyroid hormone exert a broad influence on brain development and then on adult brain physiology. However, the cell-autonomous function of the receptors is combined with their indirect influence on cellular interactions. Mouse genetics allows one to distinguish between these 2 modes of action.

Thyroid hormone action during GABAergic neuron maturation: The quest for mechanisms.

Thyroid hormone (TH) signaling plays a major role in mammalian brain development. Data obtained in the past years in animal models have pinpointed GABAergic neurons as a major target of TH signaling during development, which opens up new perspectives to further investigate the mechanisms by which TH affects brain development. The aim of the present review is to gather the available information about the involvement of TH in the maturation of GABAergic neurons.

Neuronal Blockade of Thyroid Hormone Signaling Increases Sensitivity to Diet-Induced Obesity in Adult Male Mice.

Thyroid hormone increases energy expenditure. Its action is mediated by TR, nuclear receptors present in peripheral tissues and in the central nervous system, particularly in hypothalamic neurons. Here, we address the importance of thyroid hormone signaling in neurons, in general for the regulation of energy expenditure.

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice.

Thyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model.

Prenatal exposure to paraquat and nanoscaled TiO aerosols alters the gene expression of the developing brain.

Nanopesticides are innovative pesticides involving engineered nanomaterials in their formulation to increase the efficiency of plant protection products, while mitigating their environmental impact. Despite the predicted growth of the nanopesticide use, no data is available on their inhalation toxicity and the potential cocktail effects between their components. In particular, the neurodevelopmental toxicity caused by prenatal exposures might have long lasting consequences.

A Pivotal Genetic Program Controlled by Thyroid Hormone during the Maturation of GABAergic Neurons.

Mammalian brain development critically depends on proper thyroid hormone signaling, via the TRα1 nuclear receptor. The downstream mechanisms by which TRα1 impacts brain development are currently unknown. In order to investigate these mechanisms, we used mouse genetics to induce the expression of a dominant-negative mutation of TRα1 specifically in GABAergic neurons, the main inhibitory neurons in the brain.

Regulation of T3 Availability in the Developing Brain: The Mouse Genetics Contribution.

Alterations in maternal thyroid physiology may have deleterious consequences on the development of the fetal brain, but the underlying mechanisms remain elusive, hampering the development of appropriate therapeutic strategies. The present review sums up the contribution of genetically modified mouse models to this field. In particular, knocking out genes involved in thyroid hormone (TH) deiodination, transport, and storage has significantly improved the picture that we have of the economy of TH in the fetal brain and the underlying genetic program.

CRISPR/Cas9 Editing of the Mouse Thra Gene Produces Models with Variable Resistance to Thyroid Hormone.

Background: Resistance to thyroid hormone due to THRA mutations (RTHα) is a recently discovered genetic disease, displaying important variability in its clinical presentation. The mutations alter the function of TRα1, one of the two nuclear receptors for thyroid hormone.

Methods: The aim of this study was to understand the relationship between specific THRA mutations and phenotype.

Genetic Investigation of Thyroid Hormone Receptor Function in the Developing and Adult Brain.

Thyroid hormones exert a broad influence on brain development and function, which has been extensively studied over the years. Mouse genetics has brought an important contribution, allowing precise analysis of the interplay between TRα1 and TRβ1 nuclear receptors in neural cells. However, the exact contribution of each receptor, the possible intervention of nongenomic signaling, and the nature of the genetic program that is controlled by the receptors remain poorly understood.

Deciphering direct and indirect influence of thyroid hormone with mouse genetics.

T3, the active form of thyroid hormone, binds nuclear receptors that regulate the transcription of a large number of genes in many cell types. Unraveling the direct and indirect effect of this hormonal stimulation, and establishing links between these molecular events and the developmental and physiological functions of the hormone, is a major challenge. New mouse genetics tools, notably those based on Cre/loxP technology, are suitable to perform a multiscale analysis of T3 signaling and achieve this task.

Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development.

Thyroid hormone is necessary for normal development of the central nervous system, as shown by the severe mental retardation syndrome affecting hypothyroid patients with low levels of active thyroid hormone. The postnatal defects observed in hypothyroid mouse cerebellum are recapitulated in mice heterozygous for a dominant-negative mutation of Thra, the gene encoding the ubiquitous TRα1 receptor. Using CRE/loxP-mediated conditional expression approach, we found that this mutation primarily alters the differentiation of Purkinje cells and Bergmann glia, two cerebellum-specific cell types.

Fine mapping of complex traits in non-model species: using next generation sequencing and advanced intercross lines in Japanese quail.

Background: As for other non-model species, genetic analyses in quail will benefit greatly from a higher marker density, now attainable thanks to the evolution of sequencing and genotyping technologies. Our objective was to obtain the first genome wide panel of Japanese quail SNP (Single Nucleotide Polymorphism) and to use it for the fine mapping of a QTL for a fear-related behaviour, namely tonic immobility, previously localized on Coturnix japonica chromosome 1. To this aim, two reduced representations of the genome were analysed through high-throughput 454 sequencing: AFLP (Amplified Fragment Length Polymorphism) fragments as representatives of genomic DNA, and EST (Expressed Sequence Tag) as representatives of the transcriptome.

Non PCR-amplified Transcripts and AFLP fragments as reduced representations of the quail genome for 454 Titanium sequencing.

Background: SNP (Single Nucleotide Polymorphism) discovery is now routinely performed using high-throughput sequencing of reduced representation libraries. Our objective was to adapt 454 GS FLX based sequencing methodologies in order to obtain the largest possible dataset from two reduced representations libraries, produced by AFLP (Amplified Fragment Length Polymorphism) for genomic DNA, and EST (Expressed Sequence Tag) for the transcribed fraction of the genome.

Findings: The expressed fraction was obtained by preparing cDNA libraries without PCR amplification from quail embryo and brain.

Changes in Heart Rate Variability during a tonic immobility test in quail.

Tonic immobility (TI) is an unlearned fear response induced by a brief physical restraint and characterized by a marked autonomic nervous system involvement. This experiment aimed at studying the relative involvement of both autonomic sub-systems, the sympathetic and parasympathetic nervous systems, during TI, by analyzing Heart Rate Variability. Quail selected genetically for long (LTI) or short (STI) TI duration and quail from a control line (CTI) were used.

Exploration of the hypothalamic-pituitary-adrenal function as a tool to evaluate animal welfare.

Measuring HPA axis activity is the standard approach to the study of stress and welfare in farm animals. Although the reference technique is the use of blood plasma to measure glucocorticoid hormones (cortisol or corticosterone), several alternative methods such as the measurement of corticosteroids in saliva, urine or faeces have been developed to overcome the stress induced by blood sampling itself. In chronic stress situations, as is frequently the case in studies about farm animal welfare, hormonal secretions are usually unchanged but dynamic testing allows the demonstration of functional changes at several levels of the system, including the sensitization of the adrenal cortex to ACTH and the resistance of the axis to feedback inhibition by corticosteroids (dexamethasone suppression test).

Activation of the parabrachio-amygdaloid pathway by immune challenge or spinal nociceptive input: a quantitative study in the rat using Fos immunohistochemistry and retrograde tract tracing.

Peripheral nociceptive stimulation results in activation of neurons in the pontine parabrachial nucleus (PB) of rats. Electrophysiological studies have suggested that noxiously activated PB neurons project to the amygdala, constituting a potential pathway for emotional aspects of pain. In the present study we examined this hypothesis by combining retrograde tract tracing with Fos immunohistochemistry.

Distribution of corticotropin-releasing factor-immunoreactive neurons in the central nervous system of the domestic chicken and Japanese quail.

In birds, as in mammals, corticotropin-releasing factor (CRF) is present in a number of extrahypothalamic brain regions, indicating that CRF may play a role in physiological and behavioral responses other than the control of adrenocorticotropin hormone release by the pituitary. To provide a foundation for investigation of the roles of CRF in the control of avian behavior, the distribution of CRF immunoreactivity was determined throughout the central nervous system of the domestic chicken (Gallus domesticus) and Japanese quail (Coturnix japonica). The distribution of CRF-immunoreactive (-ir) perikarya and fibers in the chicken and quail brain was found to be more extensive than previously reported, notably in the telencephalon.