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1.
J Vet Med Educ ; : e20220071, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36724159

RESUMO

A global survey was developed to gain insight into the opinion of companion animal veterinarians about their undergraduate education and their access to continuing education on the following topics: client communication, animal welfare, surgical techniques, human-animal bond, dentistry, animal behavior, and zoonotic disease/epidemiology. In 2016, the survey was distributed via SurveyMonkey® in five languages to companion animal veterinarians around the world. A total of 1,167 respondents returned to the survey. The distribution of survey responses differed by geographic region (number of respondents in parentheses; where respondents work/have been trained): Europa (including the Russian Federation, 359/423), Asia (311/205), North America (77/89), South America (24/16), Africa (46/41), and Oceania (147/167). The results were strongly influenced by a large number of respondents (in parentheses) who graduated in the Russian Federation (180/162), Australia (133/154), Israel (136/82), the Netherlands (64/64), the United Kingdom of Great Britain and Northern Ireland (36/46), and the United States of America (46/44). On the basis of the responses, all topics were poorly covered or not taught, except for surgical techniques and zoonotic disease/epidemiology, which were covered adequately or well. However, there were country and geographic regional differences. This was also true for continuing education resources, which were-in addition to countries and geographic regions-also influenced by the educational topic. As already stated by Dhein and Menon in 2003, time away from the practice, travel distance, and expense may be reasons why companion animal veterinarians do not follow continuing education. Online continuing education could fill in the gap and is more time and cost-efficient.

2.
Front Vet Sci ; 9: 939534, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483490

RESUMO

Measuring physiological parameters of stress in horses during groundwork, for example when involved in equine-assisted interventions, is important to gain insight into the stress levels of the horses. Heart rate and heart rate variability can be used as physiological indicators of stress in horses. Heart rate monitors could be easily incorporated into practice, as they are not expensive and easy to use. However, it is questionable whether heart rate monitors present accurate heart rate variability results in exercising horses, similar to electrocardiograms. The aim of this study was to determine the accuracy of heart rate monitors for the assessment of heart rate variability in horses during groundwork exercise. Simultaneous telemetric electrocardiograms (Televet) and heart rate monitor (Polar H10 transmitter and M430 receiver, Hylofit electrodes) recordings were performed on 28 horses (15 mares and 13 geldings). Results indicate that the heart rate monitor accurately determined heart rate and time-domain heart rate variability parameters when compared to electrocardiograms during both baseline and groundwork conditions. As expected, heart rate significantly increased and the heart rate variability significantly decreased during groundwork compared to baseline conditions. This indicates that the heart rate monitor can be used to accurately determine heart rate variability during groundwork.

3.
J Appl Anim Welf Sci ; : 1-48, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35502812

RESUMO

As part of a wider research on animal welfare, a global survey was developed to gain insight into the opinion of companion animal veterinarians about animal welfare education, namely to investigate i) their exposure to animal welfare teaching during their undergraduate education, ii) their access to continuing professional education on animal welfare, and iii) their opinions on clients' sources of information on animal welfare. The survey was distributed to companion animal veterinarians around the world. The results were highly influenced by the large numbers of respondents who trained in the Russian Federation, Australia, Israel, the Netherlands, the United Kingdom of Great Britain and Northern Ireland, or the United States of America. Worldwide, 58.4% of the respondents thought that animal welfare was poorly covered or not taught at all when they were students. The best coverage of animal welfare was in the Netherlands and the United Kingdom of Great Britain and Northern Ireland. Most companion animal veterinarians (65.3%) had access to continuing education on animal welfare, but there were small differences between the six above-mentioned countries. Companion animal veterinarians get information on animal welfare mainly from the internet and veterinary conferences/meetings, and thought that their clients obtained animal welfare information from various sources. The findings show that there is a need to improve education on animal welfare in veterinary curricula and the provision of relevant continuing education, so that companion animal practitioners can keep abreast of developments and societal expectations.

4.
PLoS One ; 16(8): e0255521, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34351958

RESUMO

Inter-individual variability in quantitative traits is believed to potentially inflate the quality of results in animal experimentation. Yet, to our knowledge this effect has not been empirically tested. Here we test whether inter-individual variability in emotional response within mouse inbred strains affects the outcome of a pharmacological experiment. Three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, five consecutive trials). A multivariate clustering procedure yielded two multidimensional response types which were displayed by individuals of all three strains. We show that systematic incorporation of these individual response types in the design of a pharmacological experiment produces different results from an experimental pool in which this variation was not accounted for. To our knowledge, this is the first study that empirically confirms that inter-individual variability affects the interpretation of behavioral phenotypes and may obscure experimental results in a pharmacological experiment.


Assuntos
Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Dexmedetomidina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Experimentação Animal , Animais , Ansiedade/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Especificidade da Espécie
5.
Physiol Behav ; 239: 113503, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153326

RESUMO

Inter-individual variability in behavioral and physiological response has become a well-established phenomenon in animal models of anxiety and other disorders. Such variability is even demonstrated within mouse inbred strains. A recent study showed that adaptive and non-adaptive anxiety phenotypes (measured as habituation and/or sensitization of anxiety responses) may differ within cohorts of 129 mice. This variability was expressed across both anxiety- and activity-related behavioral dimensions. These findings were based however on re-analysis of previously published data. The present study therefore aimed to empirically validate these findings in 129 mice. In addition, we assessed such inter-individuality in two other strains: BALB/c and C57BL/6. Males of three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, 4 consecutive trials). Behavioral observations were supplemented with assessment of circulating corticosterone levels. Clustering the individual response trajectories of behavioral and endocrine responses yielded two multidimensional response types of different adaptive value. Interestingly, these response types were displayed by individuals of all three strains. The response types differed significantly on anxiety and activity related behavioral dimensions but not on corticosterone concentrations. This study empirically confirms that adaptive capacities may differ within 129 cohorts. In addition, it extends this inter-individual variability in behavioral profiles to BALB/c and C57BL/6. Whether these two sub-types constitute differential anxiety phenotypes may differ per strain and requires further study.


Assuntos
Comportamento Exploratório , Habituação Psicofisiológica , Animais , Ansiedade , Comportamento Animal , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Especificidade da Espécie
6.
Animals (Basel) ; 10(9)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32917047

RESUMO

When non-human animals are labeled as 'pests', their moral status and welfare seem relatively unimportant. In a multi-stakeholder project, we develop an assessment frame for a more responsible rodent management that includes animal welfare. An online survey among 129 Dutch pest controllers was carried out in order to find out more about pest controllers' attitudes about animal welfare. Respondents indicate to consider animal welfare in their job. They see differences in the welfare impact of different rodent control methods. A dilemma may occur when methods with a high impact, such as rodenticides, are ofttimes used in practice. Respondents also indicate that in different real-life scenarios (the hospital kitchen vs. the private backyard), a different weight may be attributed to the importance of animal welfare. Almost half of the respondents encounter difficulties when weighing animals against human interests. The problems are mainly related to clients who are not willing to invest sufficient money in preventive methods, where respondents do believe in. Some differences were found between respondents depending on membership of a professional association for pest controllers. The results of this study are relevant input for focus groups with pest controllers and their clients and for the development of the aforementioned assessment frame.

7.
J Neurosci Methods ; 343: 108810, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574640

RESUMO

BACKGROUND: Despite extensive environmental standardization and the use of genetically and microbiologically defined mice of similar age and sex, individuals of the same mouse inbred strain commonly differ in quantitative traits. This is a major issue as it affects the quality of experimental results. Standard analysis practices summarize numerical data by means and associated measures of dispersion, while individual values are ignored. Perhaps taking individual values into account in statistical analysis may improve the quality of results. NEW METHOD: The present study re-inspected existing data on emotional reactivity profiles in 125 BALB/cJ and 129 mice, which displayed contrasting patterns of habituation and sensitization when repeatedly exposed to a novel environment (modified Hole Board). Behaviors were re-analyzed on an individual level, using a multivariate approach, in order to explore whether this yielded new information regarding subtypes of response, and their expression between and within strains. RESULTS: Clustering individual mice across multiple behavioral dimensions identified two response profiles: a habituation and a sensitization cluster. COMPARISON WITH EXISTING METHOD(S): These retrospect analyses identified habituation and sensitization profiles that were similar to those observed in the original data but also yielded new information such as a more pronounced sensitization response. Also, it allowed for the identification of individuals that deviated from the predominant response profile within a strain. CONCLUSIONS: The present approach allows for the behavioral characterization of experimental animals on an individual level and as such provides a valuable contribution to existing approaches that take individual variation into account in statistical analysis.


Assuntos
Camundongos Endogâmicos BALB C , Animais , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Fenótipo
8.
Animals (Basel) ; 9(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100924

RESUMO

The Monash Dog-Owner Relationship Scale (MDORS) is a questionnaire that is used to evaluate the perceived relationship between humans and their dog. This questionnaire was originally only formulated and validated in English, which limits its use among non-English speaking individuals. Although a translation could be made, the translation of questionnaires without additional validation often impairs the reliability of that questionnaire. Therefore, the aim of this study was to validate a translation of the MDORS that is suitable for use among native Dutch speakers. To achieve this, a Dutch translation of the MDORS was made and checked for spelling/grammar mistakes, readability, feasibility, and clarity. A test-retest comparison was subsequently performed on the translation together with a calculation of Cronbach's alpha score and principal component analysis (PCA). Through the PCA, we found that the three-factor model of the original MDORS was also largely present in the Dutch translation. However, deviations were also found, as several questions did not achieve high PCA scores in their original factor. Therefore, we propose that these questions are excluded from the Dutch MDORS.

9.
BMC Vet Res ; 14(1): 221, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29986701

RESUMO

BACKGROUND: This study investigated whether the body condition score (BCS) and/or culture influences the quality of life (QoL) of dogs, as evaluated by the owner, and whether the BCS is influenced by feeding and exercise and its owner's culture. To this end, a questionnaire was administered to 355 selected dog owners (Thai and Dutch). Their dogs had a BCS of 3 (normal weight), 4 (overweight) or 5 (obese) but no other physical problems. Instead of using Likert scales, continuous scales were used. Further, data for the questionnaire items were transformed using an integrated z-score methodology. RESULTS: The magnitude of factor loadings was similar to that reported in a previous study, indicating that the questionnaire is not culture specific. QoL scores for general sickness were significantly higher (worse) in dogs with a higher BCS. Thus even though the dogs were apparently healthy, the BCS influenced the perceived QoL of the dog. Immobility was seen more often in dogs with a higher (poorer) BCS than in dogs with a lower (better) BCS; however, there was no clear relationship between immobility and total activity. The higher the BCS, the less owners felt in control of feeding and exercise. The BCS was higher in the dogs of owners who did not like to exercise. The Thai dogs showed more separation-related behaviour problems when their owner left home than did the Dutch dogs. CONCLUSIONS: The QoL of overweight and obese dogs is mainly influenced by the dog's physical status. The owners of dogs with a high BCS have less perceived control over feeding and exercise. Our findings indicate that owner attitudes and beliefs essentially cause obesity as a result of a lack of knowledge and perceived control.


Assuntos
Atitude , Doenças do Cão/psicologia , Obesidade/veterinária , Sobrepeso/veterinária , Qualidade de Vida , Adulto , Animais , Atitude/etnologia , Comparação Transcultural , Cães , Feminino , Humanos , Masculino , Países Baixos , Obesidade/psicologia , Sobrepeso/psicologia , Propriedade , Inquéritos e Questionários , Tailândia
10.
Vet J ; 224: 64-75, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28697878

RESUMO

Impairment of bone growth at a young age leads to dwarfism in adulthood. Dwarfism can be categorised as either proportionate, an overall size reduction without changes in body proportions, or disproportionate, a size reduction in one or more limbs, with changes in body proportions. Many forms of dwarfism are inherited and result from structural disruptions or disrupted signalling pathways. Hormonal disruptions are evident in Brooksville miniature Brahman cattle and Z-linked dwarfism in chickens, caused by mutations in GH1 and GHR. Furthermore, mutations in IHH are the underlying cause of creeper achondroplasia in chickens. Belgian blue cattle display proportionate dwarfism caused by a mutation in RNF11, while American Angus cattle dwarfism is caused by a mutation in PRKG2. Mutations in EVC2 are associated with dwarfism in Japanese brown cattle and Tyrolean grey cattle. Fleckvieh dwarfism is caused by mutations in the GON4L gene. Mutations in COL10A1 and COL2A1 cause dwarfism in pigs and Holstein cattle, both associated with structural disruptions, while several mutations in ACAN are associated with bulldog-type dwarfism in Dexter cattle and dwarfism in American miniature horses. In other equine breeds, such as Shetland ponies and Friesian horses, dwarfism is caused by mutations in SHOX and B4GALT7. In Texel sheep, chondrodysplasia is associated with a deletion in SLC13A1. This review discusses genes known to be involved in these and other forms of dwarfism in livestock.


Assuntos
Nanismo/veterinária , Gado/genética , Animais , Doenças do Desenvolvimento Ósseo/genética , Doenças do Desenvolvimento Ósseo/veterinária , Cruzamento , Bovinos/genética , Doenças dos Bovinos/genética , Galinhas/genética , Nanismo/genética , Doenças dos Cavalos/genética , Cavalos , Gado/crescimento & desenvolvimento , Mutação , Fenótipo , Doenças das Aves Domésticas/genética , Transdução de Sinais/genética , Suínos , Doenças dos Suínos/genética
11.
J Neurogenet ; 30(3-4): 306-315, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27845603

RESUMO

Substrains of the C57BL/6 inbred mouse are widely used in genetic, behavioral and physiological research, as well as models for human disease. Throughout, the choice of the respective substrain can have a large influence on experimental results. Likewise, the conditions under which experiments are performed, such as the light regime, can significantly affect the outcome of an experiment, especially when aiming at experimental behavior. Here, two commonly used mouse substrains, C57BL/6JOlaHsd and C57BL/6NCrl, were housed under either a conventional or a reverse light regime and were tested in either the light phase or the dark phase, respectively. All animals were exposed to three unconditioned anxiety-related behavior set-ups: the modified Hole Board test, the light-dark box and the elevated plus maze. Significant substrain and light regime effects were found in all three behavioral tests, with some of the latter being substrain and test specific. This signifies the importance of the choice of substrain used in for example, a mouse knockout experiment studying behavior, also in relation to light regime under which the animals are tested.


Assuntos
Comportamento Animal/fisiologia , Abrigo para Animais , Iluminação , Camundongos Endogâmicos C57BL/genética , Animais , Ansiedade/genética , Masculino , Camundongos
12.
Eur J Neurosci ; 44(11): 2950-2957, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27690330

RESUMO

Febrile seizures (FS) are the most common seizure type in children. Recurrent FS are a risk factor for developing temporal lobe epilepsy later in life and are known to have a strong genetic component. Experimental FS (eFS) can be elicited in mice by warm-air induced hyperthermia. We used this model to screen the chromosome substitution strain (CSS) panel derived from C57BL/6J and A/J for FS susceptibility and identified C57BL/6J-Chr2A /NaJ (CSS2), as the strain with the strongest FS susceptibility phenotype. The aim of this study was to map FS susceptibility loci and select candidate genes on mouse chromosome 2. We generated an F2 population by intercrossing the hybrids (F1 ) that were derived from CSS2 and C57BL/6J mice. All CSS2-F2 individuals were genotyped and phenotyped for eFS susceptibility, and QTL analysis was performed. Candidate gene selection was based on bioinformatics analyses and differential brain expression between CSS2 and C57BL/6J strains determined by microarray analysis. Genetic mapping of the eFS susceptibility trait identified two significant loci: FS-QTL2a (LOD-score 3.6) and FS-QTL2b (LOD-score 6.2). FS-QTL2a contained 44 genes expressed in the brain at post natal day 14. Four of these (Arl6ip6, Cytip, Fmnl2 Ifih1) contained a non-synonymous SNP comparing CSS2 and C57BL/6J, six genes (March7, Nr4a2, Gpd2, Grb14, Scn1a, Scn3a) were differentially expressed between these strains. A region within FS-QTL2a is homologous to the human FEB3 locus. The fact that we identify mouse FS-QTL2a with high FEB3 homology is strong support for the validity of the eFS mouse model to study genetics of human FS.


Assuntos
Canal de Sódio Disparado por Voltagem NAV1.1/genética , Canal de Sódio Disparado por Voltagem NAV1.3/genética , Locos de Características Quantitativas , Convulsões Febris/genética , Animais , Cromossomos/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polimorfismo de Nucleotídeo Único , Homologia de Sequência
13.
J Vis Exp ; (98)2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25938188

RESUMO

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal's behavioral profile can be investigated in one single test. The apparatus consists of a box, representing the 'protected' area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the 'unprotected' area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals' adaptive capacities. Due to testing order effects in a behavioral test battery, naïve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.


Assuntos
Comportamento Animal , Cognição/fisiologia , Comportamento Exploratório , Comportamento Social , Animais , Ansiedade/psicologia , Memória , Camundongos , Camundongos Endogâmicos BALB C , Ratos
14.
BMC Res Notes ; 8: 128, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25889519

RESUMO

BACKGROUND: An important risk for atherosclerosis is a low level of HDL cholesterol. Baseline HDL cholesterol is under complex genetic and environmental control. Here we report on results of male mice from a consomic strain survey and the parental inbred strains for baseline circulating total cholesterol concentration, which is almost the same as HDL cholesterol in chow fed mice. The consomic strains have been derived from C57BL/6J (host strain) and A/J (donor strain) inbred lines. The work contributes to the value of the mouse as an animal model for studying the genetic background of differences in baseline circulating total and HDL cholesterol levels. RESULTS: The consomic strain survey suggested that mouse chromosomes 1, 7, 9, 14, 16, 17, 19, X, and Y contained at least one quantitative trait locus that is involved in baseline circulating total cholesterol concentration. All consomic lines, for which there is evidence that the substituted chromosome contains a quantitative trait locus, increase compared to the host strain baseline circulating total cholesterol concentration. Since there is evidence that 'body weight', 'age at blood sampling', 'time of the day blood was collected', and 'season' influence this phenotype, additional statistical analyses (with these variables as covariates) were performed. Now there is only evidence for quantitative trait loci on chromosomes 1, 8, 12, and Y. Taken the present results together with previous consomic strain surveys there is evidence that all mouse chromosomes carry quantitative trait loci that control baseline circulating total cholesterol levels. There was however little agreement between the present consomic strain results and previous sets of data. This might be explained by seasonal effects and differences in methodological variables such as age of the mice, fasting versus non-fasting, percentage of dietary fat, unanesthetized versus anesthetized mice, and the daily light-dark cycle. CONCLUSIONS: The present findings, when compared with previous consomic strain surveys, clearly illustrate the complexity of the genetic-environmental architecture for the regulation of baseline circulating total cholesterol levels in mice. Different data can be obtained from different labs and it underscores that animal geneticists should present as accurate a picture as possible of the laboratory mouse's environment.


Assuntos
HDL-Colesterol/genética , Cromossomos/química , Locos de Características Quantitativas , Fatores Etários , Animais , Peso Corporal , HDL-Colesterol/sangue , Mapeamento Cromossômico , Cruzamentos Genéticos , Interação Gene-Ambiente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Fotoperíodo , Estações do Ano , Fatores de Tempo
15.
Biol Psychiatry ; 78(7): 485-95, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25802080

RESUMO

BACKGROUND: Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development. METHODS: Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology. RESULTS: Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed. CONCLUSIONS: This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes.


Assuntos
Atividade Motora/fisiologia , Reconhecimento Psicológico/fisiologia , Córtex Sensório-Motor/patologia , Filtro Sensorial/fisiologia , Percepção Social , Animais , Aprendizagem por Associação/fisiologia , Mapeamento Cromossômico , Cognição/fisiologia , Dendritos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Fenótipo , Locos de Características Quantitativas , Córtex Sensório-Motor/crescimento & desenvolvimento , Córtex Sensório-Motor/fisiopatologia , Filtro Sensorial/genética
16.
Eur J Neurosci ; 40(1): 2311-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24674448

RESUMO

How external stimuli prevent the onset of sleep has been little studied. This is usually considered to be a non-specific type of phenomenon. However, the hypnotic drug dexmedetomidine, an agonist at α2 adrenergic receptors, has unusual properties that make it useful for investigating this question. Dexmedetomidine is considered to produce an 'arousable' sleep-like state, so that patients or animals given dexmedetomidine become alert following modest stimulation. We hypothesized that it might be more difficult to make mice unconscious with dexmedetomidine if there was a sufficient external stimulus. Employing a motorized rotating cylinder, which provided a continuous and controlled arousal stimulus, we quantitatively measured the ability of such a stimulus to prevent dexmedetomidine loss of righting reflex in two inbred strains of mice (C57BL/6 and 129X1). We found that whereas the C57BL/6 strain required a strong stimulus to prevent dexmedetomidine-induced hypnosis, the 129X1 strain stayed awake even with minimal stimuli. Remarkably, this could be calibrated as a simple threshold trait, i.e. a binary 'yes-no' response, which after crossing the two mouse strains behaved as a dominant-like trait. We carried out a genome-wide linkage analysis on the F2 progeny to determine if the ability of a stimulus to prevent dexmedetomidine hypnosis could be mapped to one or more chromosomal regions. We identified a locus on chromosome 4 with an associated Logarithm of Odds score exceeding the pre-established threshold level. These results show that complex traits, such as the ability of a stimulus to reverse drug-induced hypnosis, may have precise genetic determinants.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Dexmedetomidina/farmacologia , Sono/genética , Vigília/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Cromossomos de Mamíferos , Eletroencefalografia , Genes Dominantes , Estudo de Associação Genômica Ampla , Hipnóticos e Sedativos/farmacologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Farmacogenética , Estimulação Física , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo , Reflexo de Endireitamento/efeitos dos fármacos , Reflexo de Endireitamento/genética , Reflexo de Endireitamento/fisiologia , Teste de Desempenho do Rota-Rod , Sono/efeitos dos fármacos , Sono/fisiologia , Especificidade da Espécie , Vigília/efeitos dos fármacos , Vigília/fisiologia
17.
Ann Clin Transl Neurol ; 1(4): 239-50, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25590037

RESUMO

OBJECTIVE: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. METHODS: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. RESULTS: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. INTERPRETATION: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE.

18.
Epilepsia ; 53(8): 1399-410, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22780306

RESUMO

PURPOSE: Febrile seizures (FS) are the most common seizure type in children between the age of 6 months and 5 years. Although FS are largely benign, recurrent FS are a major risk factor for developing temporal lobe epilepsy (TLE) later in life. The mechanisms underlying FS are largely unknown; however, family and twin studies indicate that FS susceptibility is under complex genetic control. We have recently developed a phenotypic screen to study the genetics of FS susceptibility in mice. Using this screen in a phenotype-driven genetic strategy we analyzed the C57BL/6J-Chr #(A)/NaJ chromosome substitution strain (CSS) panel. In each CSS line one chromosome of the A/J strain is substituted in a genetically homogeneous C57BL/6J background. The analysis of the CSS panel revealed that A/J chromosomes 1, 2, 6, 10, 13, and X carry at least one quantitative trait locus (QTL) for heat-induced FS susceptibility. The fact that many X-linked genes are highly expressed in the brain and have been implicated in human developmental disorders often presenting with seizures (like fragile X mental retardation) prompted us to map the chromosome X QTL. METHODS: C57BL/6J mice were mated with C57BL/6J-Chr X(A) /NaJ (CSSX) to generate F(2)-generations-CXBL6 and BL6CX-originating from CSSX or C57BL/6J mothers, respectively. Heat-induced FS were elicited on postnatal day 14 by exposure to a controlled warm airstream of 50°C. The latency to heat-induced FS is our phenotype. This phenotype has previously been validated by video-electroencephalography (EEG) monitoring. After phenotyping and genotyping the F(2)-population, QTL analysis was performed using R/QTL software. KEY FINDINGS: QTL analysis revealed a significant peak with an LOD-score of 3.25. The 1-LOD confidence interval (149,886,866-158,836,462 bp) comprises 52 protein coding genes, of which 34 are known to be brain expressed. Two of these brain-expressed genes have previously been linked to X-linked epilepsies, namely Cdkl5 and Pdha1. SIGNIFICANCE: Our results show that the mouse genetics of X-linked FS susceptibility is complex, and that our heat-induced FS-driven genetic approach is a powerful tool for use in unraveling the complexities of this trait in mice. Fine-mapping and functional studies will be required to further identify the X-linked FS susceptibility genes.


Assuntos
Convulsões Febris/genética , Cromossomo X/genética , Animais , Mapeamento Cromossômico , Feminino , Escore Lod , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Repetições de Microssatélites/genética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase (Lipoamida)/genética , Convulsões Febris/etiologia
19.
Vet J ; 190(2): 208-214, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21195645

RESUMO

There is a widespread belief that interaction with an animal is beneficial for the development of children, and several studies (most with methodological shortcomings) have investigated the influence of (companion) animals on the social-emotional and cognitive development of children. In this article, the 1984 model of Professor Jay Belsky has been used to describe which variables influence the development of children and how the companion animal-child interaction influences these variables. The value of the AAA/AAT (Animal Assisted Activities/Animal Assisted Therapy) programmes in children with a wide variety of clinical and social problems, such as behaviour problems and autistic spectrum symptoms, is discussed. The findings suggest that (companion) animals positively influence children's development and have a valuable role in therapy.


Assuntos
Terapia Assistida com Animais , Transtornos do Comportamento Infantil/terapia , Transtornos Globais do Desenvolvimento Infantil/terapia , Desenvolvimento Infantil , Vínculo Humano-Animal , Animais , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/terapia , Criança , Transtornos do Comportamento Infantil/psicologia , Transtornos Globais do Desenvolvimento Infantil/psicologia , Humanos
20.
Physiol Behav ; 102(2): 205-19, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21036185

RESUMO

Up to 29% of all adults will experience an anxiety-related disorder during their lives. Treatment of these disorders is still difficult and the exact mechanisms and pathways behind anxiety disorders remain to be elucidated. Although evidence exists for genetically based susceptibility of human psychiatric diseases, risk genes have rarely been identified up to now. Inbred mouse strains are, together with the crosses and genetic reference populations derived from them, important tools for the genetic dissection of complex behavioral traits in the mouse. Thus, inbred mouse models of human anxiety may be a potent starting tool to search for candidate genes in mice, which could then via comparative genomics be translated to the human situation. In this paper we investigate whether the A/J and C57BL/6J mouse inbred strains differ in a limited number of motivational systems (anxiety, exploration, memory, locomotion, and social affinity), but especially in anxiety-related behavior from each other. Young adult individuals from both genders of A/J and C57BL/6J strains were behaviorally phenotyped using a multidimensional test: the modified hole board. This paradigm basically is a combination of the traditional hole board and the open field test allowing to test for anxiety-related avoidance behavior, risk assessment, arousal, exploration, memory, locomotor activity, and social affinity, using just one single test. An acute, aversive stimulus (intra-peritoneal injection with saline) was applied to the animals to test for the robustness of their behavioral phenotype. In addition, presumed physiological indicators for anxiety (circulating glucose, cholesterol, and corticosterone, adrenal tyrosine hydroxylase, and blood plasma and brain magnesium) were investigated. It could be concluded that C57BL/6J and A/J mice differ with respect to almost all tested motivational systems. For some measures, including anxiety-related behavioral parameters, there were clear gender effects. The high-anxiety phenotype of A/J mice could be shown to represent a primary and robust characteristic. Further, blood plasma and brain magnesium levels were significantly correlated with several anxiety-related behavioral parameters. These results emphasize the hypothesized, and possibly causal, association between magnesium status and emotionality.


Assuntos
Ansiedade , Comportamento Animal/fisiologia , Encéfalo/metabolismo , Magnésio/metabolismo , Plasma/metabolismo , Análise de Variância , Animais , Ansiedade/genética , Ansiedade/metabolismo , Ansiedade/patologia , Aprendizagem da Esquiva/fisiologia , Colesterol/metabolismo , Corticosterona/sangue , Modelos Animais de Doenças , Reação de Fuga/fisiologia , Comportamento Exploratório/fisiologia , Feminino , Glucose/metabolismo , Masculino , Ciclo Menstrual/genética , Camundongos , Camundongos Endogâmicos A/genética , Camundongos Endogâmicos C57BL/genética , Motivação/genética , Testes Neuropsicológicos , Radioimunoensaio/métodos , Reconhecimento Psicológico/fisiologia , Medição de Risco , Tirosina 3-Mono-Oxigenase/metabolismo , Esfregaço Vaginal
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