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1.
Brain ; 146(11): 4766-4783, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37437211

RESUMO

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.


Assuntos
Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Animais , Camundongos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Encéfalo/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Cognição , Proteínas dos Microfilamentos/genética
2.
Am J Hum Genet ; 99(2): 253-74, 2016 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-27453576

RESUMO

Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.


Assuntos
Proteínas de Transporte/genética , Haploinsuficiência/genética , Deficiência Intelectual/genética , Transtornos do Neurodesenvolvimento/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Transcrição Gênica , Animais , Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Córtex Cerebral/metabolismo , Montagem e Desmontagem da Cromatina/genética , Códon sem Sentido/genética , Transtornos Cognitivos/genética , Mutação da Fase de Leitura/genética , Hipocampo/metabolismo , Humanos , Deficiência Intelectual/patologia , Deficiência Intelectual/psicologia , Masculino , Camundongos , Microcefalia/genética , Mutação de Sentido Incorreto/genética , Transtornos do Neurodesenvolvimento/patologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Fenótipo , Proteínas Repressoras , Comportamento Social , Síndrome , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Transcriptoma
3.
Mamm Genome ; 29(5-6): 299-309, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29740698

RESUMO

High on the Heidelberg hills, inside the Advanced Training Centre of the European Molecular Biology Laboratory (EMBL) campus with its unique double-helix staircase, scientists gathered for the EMBL conference "Mammalian Genetics and Genomics: From Molecular Mechanisms to Translational Applications," organized in cooperation with the International Mammalian Genome Society (IMGS) and the Mouse Molecular Genetics (MMG) group. The conference attracted 205 participants from 30 countries, representing 6 of the 7 continents-all except Antarctica. It was a richly diverse group of geneticists, clinicians, and bioinformaticians, with presentations by established and junior investigators, including many trainees. From the 24th-27th of October 2017, they shared exciting advances in mammalian genetics and genomics research, from the introduction of cutting-edge technologies to descriptions of translational studies involving highly relevant models of human disease.


Assuntos
Genômica , Mamíferos/genética , Animais , Biologia Computacional/métodos , Genoma , Genômica/métodos , Humanos , Pesquisa Translacional Biomédica
4.
Chem Senses ; 41(8): 669-76, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27377750

RESUMO

In rodents, the vomeronasal system controls social and sexual behavior. However, several mechanistic aspects of sensory signaling in the vomeronasal organ remain unclear. Here, we investigate the biophysical basis of a recently proposed vomeronasal signal transduction component-a Ca(2+)-activated Cl(-) current. As the physiological role of such a current is a direct function of the Cl(-) equilibrium potential, we determined the intracellular Cl(-) concentration in dendritic knobs of vomeronasal neurons. Quantitative fluorescence lifetime imaging of a Cl(-)-sensitive dye at the apical surface of the intact vomeronasal neuroepithelium revealed increased cytosolic Cl(-) levels in dendritic knobs, a substantially lower Cl(-) concentration in vomeronasal sustentacular cells, and an apparent Cl(-) gradient in vomeronasal neurons along their dendritic apicobasal axis. Together, our data provide a biophysical basis for sensory signal amplification in vomeronasal neuron microvilli by opening Ca(2+)-activated Cl(-) channels.


Assuntos
Cloretos/análise , Citosol/química , Dendritos/química , Células Receptoras Sensoriais/química , Órgão Vomeronasal/química , Animais , Cálcio/metabolismo , Canais de Cloreto/metabolismo , Citosol/metabolismo , Dendritos/metabolismo , Camundongos , Células Receptoras Sensoriais/metabolismo , Órgão Vomeronasal/metabolismo
5.
PLoS Genet ; 8(11): e1003022, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23166506

RESUMO

Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm)) that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm) embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm) embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.


Assuntos
Centríolos , Nanismo , Desenvolvimento Embrionário/genética , Microcefalia , Proteínas Associadas aos Microtúbulos/genética , Animais , Apoptose , Centríolos/genética , Centríolos/metabolismo , Dano ao DNA , Nanismo/genética , Nanismo/fisiopatologia , Fácies , Instabilidade Genômica , Camundongos , Camundongos Transgênicos , Microcefalia/genética , Microcefalia/fisiopatologia , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/metabolismo , Mitose/genética , Mutação , Transdução de Sinais/genética , Fuso Acromático/genética
6.
BMC Biol ; 12: 33, 2014 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-24884538

RESUMO

The vomeronasal organ, a sensory structure within the nasal cavity of most tetrapods, detects pheromones that influence socio-sexual behavior. It has two neuronal layers, each patterned by distinct receptor sub-families coupled to different G-proteins. Work recently published in this journal found female mice with one layer genetically inactivated are deficient in a surprisingly wide range of reproductive behaviors, providing new insights into how the nose can influence the brain.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Feromônios/farmacologia , Reprodução/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Feminino , Masculino
7.
Cell Tissue Res ; 354(1): 69-80, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23604803

RESUMO

Rats and mice are the most widely used species for modelling psychiatric disease. Assessment of these rodent models typically involves the analysis of aberrant behaviour with behavioural interactions often being manipulated to generate the model. Rodents rely heavily on their excellent sense of smell and almost all their social interactions have a strong olfactory component. Therefore, experimental paradigms that exploit these olfactory-mediated behaviours are among the most robust available and are highly prevalent in psychiatric disease research. These include tests of aggression and maternal instinct, foraging, olfactory memory and habituation and the establishment of social hierarchies. An appreciation of the way that rodents regulate these behaviours in an ethological context can assist experimenters to generate better data from their models and to avoid common pitfalls. We describe some of the more commonly used behavioural paradigms from a rodent olfactory perspective and discuss their application in existing models of psychiatric disease. We introduce the four olfactory subsystems that integrate to mediate the behavioural responses and the types of sensory cue that promote them and discuss their control and practical implementation to improve experimental outcomes. In addition, because smell is critical for normal behaviour in rodents and yet olfactory dysfunction is often associated with neuropsychiatric disease, we introduce some tests for olfactory function that can be applied to rodent models of psychiatric disorders as part of behavioural analysis.


Assuntos
Modelos Animais de Doenças , Transtornos Mentais/fisiopatologia , Condutos Olfatórios/fisiopatologia , Olfato/fisiologia , Animais , Humanos , Transtornos Mentais/psicologia , Camundongos , Ratos , Roedores
8.
Nat Commun ; 14(1): 3449, 2023 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301943

RESUMO

Muscle strength is highly heritable and predictive for multiple adverse health outcomes including mortality. Here, we present a rare protein-coding variant association study in 340,319 individuals for hand grip strength, a proxy measure of muscle strength. We show that the exome-wide burden of rare protein-truncating and damaging missense variants is associated with a reduction in hand grip strength. We identify six significant hand grip strength genes, KDM5B, OBSCN, GIGYF1, TTN, RB1CC1, and EIF3J. In the example of the titin (TTN) locus we demonstrate a convergence of rare with common variant association signals and uncover genetic relationships between reduced hand grip strength and disease. Finally, we identify shared mechanisms between brain and muscle function and uncover additive effects between rare and common genetic variation on muscle strength.


Assuntos
Força da Mão , Doenças Musculares , Humanos , Força Muscular/genética , Mutação de Sentido Incorreto , Predisposição Genética para Doença , Proteínas de Transporte
9.
Nat Genet ; 55(6): 927-938, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37231097

RESUMO

Compelling evidence suggests that human cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein-coding variants impact cognitive function in the adult population (n = 485,930). We identify eight genes (ADGRB2, KDM5B, GIGYF1, ANKRD12, SLC8A1, RC3H2, CACNA1A and BCAS3) that are associated with adult cognitive function through rare coding variants with large effects. Rare genetic architecture for cognitive function partially overlaps with that of neurodevelopmental disorders. In the case of KDM5B we show how the genetic dosage of one of these genes may determine the variability of cognitive, behavioral and molecular traits in mice and humans. We further provide evidence that rare and common variants overlap in association signals and contribute additively to cognitive function. Our study introduces the relevance of rare coding variants for cognitive function and unveils high-impact monogenic contributions to how cognitive function is distributed in the normal adult population.


Assuntos
Variação Genética , Transtornos do Neurodesenvolvimento , Humanos , Adulto , Animais , Camundongos , Predisposição Genética para Doença , Fenótipo , Cognição , Proteínas de Transporte/genética , Proteínas Nucleares/genética
10.
BMC Genomics ; 13: 415, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22908939

RESUMO

BACKGROUND: Vomeronasal receptors (VRs), expressed in sensory neurons of the vomeronasal organ, are thought to bind pheromones and mediate innate behaviours. The mouse reference genome has over 360 functional VRs arranged in highly homologous clusters, but the vast majority are of unknown function. Differences in these receptors within and between closely related species of mice are likely to underpin a range of behavioural responses. To investigate these differences, we interrogated the VR gene repertoire from 17 inbred strains of mice using massively parallel sequencing. RESULTS: Approximately half of the 6222 VR genes that we investigated could be successfully resolved, and those that were unambiguously mapped resulted in an extremely accurate dataset. Collectively VRs have over twice the coding sequence variation of the genome average; but we identify striking non-random distribution of these variants within and between genes, clusters, clades and functional classes of VRs. We show that functional VR gene repertoires differ considerably between different Mus subspecies and species, suggesting these receptors may play a role in mediating behavioural adaptations. Finally, we provide evidence that widely-used, highly inbred laboratory-derived strains have a greatly reduced, but not entirely redundant capacity for differential pheromone-mediated behaviours. CONCLUSIONS: Together our results suggest that the unusually variable VR repertoires of mice have a significant role in encoding differences in olfactory-mediated responses and behaviours. Our dataset has expanded over nine fold the known number of mouse VR alleles, and will enable mechanistic analyses into the genetics of innate behavioural differences in mice.


Assuntos
Variação Genética/genética , Receptores de Feromônios/genética , Órgão Vomeronasal/metabolismo , Animais , Genoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos , Polimorfismo de Nucleotídeo Único/genética
11.
Mamm Genome ; 23(11-12): 749-57, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22926222

RESUMO

Haploinsufficiency of the human 5q35 region spanning the NSD1 gene results in a rare genomic disorder known as Sotos syndrome (Sotos), with patients displaying a variety of clinical features, including pre- and postnatal overgrowth, intellectual disability, and urinary/renal abnormalities. We used chromosome engineering to generate a segmental monosomy, i.e., mice carrying a heterozygous 1.5-Mb deletion of 36 genes on mouse chromosome 13 (4732471D19Rik-B4galt7), syntenic with 5q35.2-q35.3 in humans (Df(13)Ms2Dja ( +/- ) mice). Surprisingly Df(13)Ms2Dja ( +/- ) mice were significantly smaller for their gestational age and also showed decreased postnatal growth, in contrast to Sotos patients. Df(13)Ms2Dja ( +/- ) mice did, however, display deficits in long-term memory retention and dilation of the pelvicalyceal system, which in part may model the learning difficulties and renal abnormalities observed in Sotos patients. Thus, haploinsufficiency of genes within the mouse 4732471D19Rik-B4galt7 deletion interval play important roles in growth, memory retention, and the development of the renal pelvicalyceal system.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5/genética , Modelos Animais de Doenças , Crescimento e Desenvolvimento/genética , Transtornos da Memória/genética , Síndrome de Sotos/genética , Absorciometria de Fóton , Animais , Southern Blotting , Pesos e Medidas Corporais , Hibridização Genômica Comparativa , Primers do DNA/genética , Marcação de Genes/métodos , Haploinsuficiência/genética , Técnicas Histológicas , Humanos , Hibridização in Situ Fluorescente , Rim/anormalidades , Camundongos , Síndrome de Sotos/patologia
12.
Science ; 362(6419): 1161-1164, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30409806

RESUMO

We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.


Assuntos
Deficiências do Desenvolvimento/genética , Genes Recessivos , Código Genético , Variação Genética , Penetrância , Animais , Modelos Animais de Doenças , Fator de Iniciação 3 em Eucariotos/genética , Europa (Continente) , Estudo de Associação Genômica Ampla , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Proteínas Nucleares/genética , Paquistão , Filogenia , Proteínas Repressoras/genética
13.
Front Behav Neurosci ; 8: 193, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24926241

RESUMO

Neural plasticity changes within the olfactory bulb are important for olfactory learning, although how neural encoding changes support new associations with specific odors and whether they can be investigated under anesthesia, remain unclear. Using the social transmission of food preference olfactory learning paradigm in mice in conjunction with in vivo microdialysis sampling we have shown firstly that a learned preference for a scented food odor smelled on the breath of a demonstrator animal occurs under isofluorane anesthesia. Furthermore, subsequent exposure to this cued odor under anesthesia promotes the same pattern of increased release of glutamate and gamma-aminobutyric acid (GABA) in the olfactory bulb as previously found in conscious animals following olfactory learning, and evoked GABA release was positively correlated with the amount of scented food eaten. In a second experiment, multiarray (24 electrodes) electrophysiological recordings were made from olfactory bulb mitral cells under isofluorane anesthesia before, during and after a novel scented food odor was paired with carbon disulfide. Results showed significant increases in overall firing frequency to the cued-odor during and after learning and decreases in response to an uncued odor. Analysis of patterns of changes in individual neurons revealed that a substantial proportion (>50%) of them significantly changed their response profiles during and after learning with most of those previously inhibited becoming excited. A large number of cells exhibiting no response to the odors prior to learning were either excited or inhibited afterwards. With the uncued odor many previously responsive cells became unresponsive or inhibited. Learning associated changes only occurred in the posterior part of the olfactory bulb. Thus olfactory learning under anesthesia promotes extensive, but spatially distinct, changes in mitral cell networks to both cued and uncued odors as well as in evoked glutamate and GABA release.

14.
PLoS One ; 7(1): e29681, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22276124

RESUMO

Haploinsufficiency of part of human chromosome 21 results in a rare condition known as Monosomy 21. This disease displays a variety of clinical phenotypes, including intellectual disability, craniofacial dysmorphology, skeletal and cardiac abnormalities, and respiratory complications. To search for dosage-sensitive genes involved in this disorder, we used chromosome engineering to generate a mouse model carrying a deletion of the Lipi-Usp25 interval, syntenic with 21q11.2-q21.1 in humans. Haploinsufficiency for the 6 genes in this interval resulted in no gross morphological defects and behavioral analysis performed using an open field test, a test of anxiety, and tests for social interaction were normal in monosomic mice. Monosomic mice did, however, display impaired memory retention compared to control animals. Moreover, when fed a high-fat diet (HFD) monosomic mice exhibited a significant increase in fat mass/fat percentage estimate compared with controls, severe fatty changes in their livers, and thickened subcutaneous fat. Thus, genes within the Lipi-Usp25 interval may participate in memory retention and in the regulation of fat deposition.


Assuntos
Deleção Cromossômica , Dieta Hiperlipídica , Haploinsuficiência/fisiologia , Absorciometria de Fóton , Animais , Comportamento Animal , Southern Blotting , Linhagem Celular , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 21/metabolismo , Feminino , Haploinsuficiência/genética , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Aprendizagem em Labirinto , Camundongos , Monossomia/genética , Reconhecimento Psicológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Behav Brain Res ; 200(2): 323-35, 2009 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-19150375

RESUMO

There is increasing evidence for specialised processing of social cues in the brain. This review considers how the main olfactory system of mammals is designed to process social odours and the effects of learning in a social context. It focuses mainly on extensive research carried out on offspring, mate or conspecific learning carried out in sheep and rodents. Detailing the roles of the olfactory bulb and its projections, classical neurotransmitters, nitric oxide, oestrogen and neuropeptides such as oxytocin and vasopressin in mediating plasticity changes in the olfactory system arising from these different social learning contexts. The relative simplicity of the organisation of the olfactory system, the speed and robustness of these forms of social learning together with the similarity in brain regions and neurochemical contributions across the different learning paradigms make them important and useful models for investigating general principles of learning and memory in the brain.


Assuntos
Aprendizagem , Condutos Olfatórios/fisiologia , Roedores/fisiologia , Comportamento Social , Animais , Animais Recém-Nascidos/fisiologia , Animais Recém-Nascidos/psicologia , Preferências Alimentares/fisiologia , Hormônios Gonadais/fisiologia , Odorantes , Condutos Olfatórios/anatomia & histologia , Receptores de Estrogênio/genética , Reconhecimento Psicológico/fisiologia , Comportamento Sexual Animal/fisiologia , Ovinos/fisiologia
16.
J Reprod Dev ; 51(5): 547-58, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16284449

RESUMO

Our work with both sheep and mouse models has revealed many of the neural substrates and signalling pathways involved in olfactory recognition memory in the main olfactory system. A distributed neural system is required for initial memory formation and its short-term retention-the olfactory bulb, piriform and entorhinal cortices and hippocampus. Following memory consolidation, after 8 h or so, only the olfactory bulb and piriform cortex appear to be important for effective recall. Similarly, whereas the glutamate-NMDA/AMPA receptor-nitric oxide (NO)-cyclic GMP signalling pathway is important for memory formation it is not involved in recall post-consolidation. Here, within the olfactory bulb, up-regulation of class 1 metabotropic glutamate receptors appears to maintain the enhanced sensitivity at the mitral to granule cell synapses required for effective memory recall. Recently we have investigated whether fluctuating sex hormone levels during the oestrous cycle modulate olfactory recognition memory and the different neural substrates and signalling pathways involved. These studies have used two robust models of social olfactory memory in the mouse which either involve social or non social odours (habituation-dishabituation and social transmission of food preference tasks). In both cases significant improvement of learning retention occurs when original learning takes place during the proestrus phase of the ovarian cycle. This is probably the result of oestrogen changes at this time since transgenic mice lacking functional expression of oestrogen receptors (ERalpha and ERbeta, the two main oestrogen receptor sub-types) have shown problems in social recognition. Therefore, oestrogen appears to act at the level of the olfactory bulb by modulating both noradrenaline and the glutamate/NO signalling pathway.


Assuntos
Aprendizagem por Discriminação/fisiologia , Memória/fisiologia , Condutos Olfatórios/fisiologia , Animais , Ciclo Estral/fisiologia , Feminino , Camundongos , Odorantes , Bulbo Olfatório/fisiologia , Receptores de AMPA/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Ovinos
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