PubMed Health⌕ Search

Biomedical subjects

Wim E Crusio

Publications and source records attributed to Wim E Crusio.

At least 19 recordsLinked to original sources
PubMed2006

Effects of unpredictable chronic mild stress on anxiety and depression-like behavior in mice.

The widely accepted stress-diathesis hypothesis of depression postulates that genetic factors contribute to biological vulnerability. Based on this concept, the unpredictable chronic mild stress (UCMS) animal model was developed. Most effects of UCMS can be reversed by antidepressant agents, illustrating a strong predictive validity. In rodents, UCMS also has good face validity as it can elicit depression-like symptoms. While abundant for rats, the UCMS literature on mice is relatively limited. Reports sometimes are contradictory, making it difficult to establish a clear profile of stress-induced depression-like behaviors in mice. As different groups often use different strains for their experiments, differential strain susceptibility to UCMS may provide at least a partial explanation of these discrepancies. Moreover, differences in testing methodology add another level of complexity. Very little is known about the role of genetic factors and their interactions with the environment in the development of stress-induced behavioral changes relevant to depression, though recent studies unequivocally demonstrated the effects of specific gene polymorphisms on stress-induced depressive symptoms, as well as the effects of stress on gene expression. In the present study, we investigated the effects of UCMS on a battery of different tests measuring anxiety and depression-like behaviors in three behaviorally and genetically distinct inbred strains. The goals of these experiments are to obtain a clearer behavioral profile of genetically/phenotypically distant mouse strains after UCMS treatment and to evaluate the limitations and strengths of the UCMS model in mice.

Analysis of Variance↗
PubMed2006

Fmr1 KO mice as a possible model of autistic features.

Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude that Fmr1 KO mice display several autistic-like features, but more work is needed to validate this model.

Animals↗
PubMed2006

Antidepressant-like effects of the histone deacetylase inhibitor, sodium butyrate, in the mouse.

BACKGROUND: Chromatin remodeling, including changes in histone acetylation, might play a role in the pathophysiology and treatment of depression. We investigated whether the histone deacetylase inhibitor sodium butyrate (SB) administered as single drug or in combination with the selective serotonin reuptake inhibitor (SSRI) fluoxetine exerts antidepressant-like effects in mice. METHODS: Mice (C57BL/6J) received injections of SB, fluoxetine, or a combination of both drugs either acutely or chronically for a period of 28 days and were subjected to a battery of tests to measure anxiety and behavioral despair. Histone acetylation and expression of brain-derived neurotrophic factor (BDNF) were monitored in hippocampus and frontal cortex. RESULTS: Co-treatment with SB and fluoxetine resulted in a significant 20%-40% decrease in immobility scores in the tail suspension test (TST), a measure for behavioral despair, both acutely and chronically. In contrast, decreased immobility after single drug regimens was limited either to the acute (fluoxetine) or chronic (SB) paradigm. Systemic injection of SB induced short-lasting histone hyperacetylation in hippocampus and frontal cortex. Among the four treatment paradigms that resulted in improved immobility scores in the TST, three were associated with a transient, at least 50% increase in BDNF transcript in frontal cortex, whereas changes in hippocampus were less consistent. CONCLUSIONS: The histone deacetylase inhibitor SB exerts antidepressant-like effects in the mouse. The therapeutic benefits and molecular actions of histone modifying drugs, including co-treatment with SSRIs and other newer generation antidepressant medications, warrant further exploration in experimental models.

Animals↗
PubMed2006

Inheritance of behavioral and neuroanatomical phenotypical variance: hybrid mice are not always more stable than inbreds.

Many investigators have attempted to confirm the prediction that increased levels of heterozygosity entail greater developmental stability, manifesting itself through decreased phenotypical variation. The evidence presented so far is equivocal. The predicted relationship has been found in some morphological studies, but not in others. I propose that the variability of a character should be seen as different from the character itself. For most morphological characters, natural selection promotes strong canalization of development but, to facilitate responses to environmental changes, the organism needs to retain malleability of physiological and behavioral traits. These different types of selection should lead to distinct genetic architectures for these phenotypes. I report on the results of a diallel cross between four inbred mouse strains. Qualitatively different genetic architectures were in fact revealed for variation in behaviors in the open-field. In a second study, variances of inbred and hybrid populations for hippocampal morphometry were studied. Again, hybrids were not always less variable than inbreds and sometimes even more variable. It follows that there exists no one-to-one relation between heterozygosity and developmental stability.

Animals↗
PubMed2005

Social behavior deficits in the Fmr1 mutant mouse.

Mice exhibiting deficits in social behavior may provide valuable models for autistic-like behavioral problems. We tested social interactions in male mice from three inbred strains: C57BL/6J (B6), BALB/cJ (C) and DBA/2J (D2). All three strains showed gradual habituation of the number of social interactions with an ovariectomized female over four subsequent 2min sessions, returning to initial levels when presented with another stimulus mouse. Next, we studied males with a knockout mutation in the Fmr1 gene on a B6 background. KO animals showed strongly reduced levels of social interaction, which were about similar as those of habituated controls. This social behavior deficit suggests that Fmr1 KO mice could possibly be used as models for autistic behaviors.

Animals↗
PubMed2005

Ovarian abnormalities in the staggerer mutant mouse.

Disturbances in several reproductive functions of the staggerer cerebellar mutant mouse have been observed. In this study, reproductive efficiency of staggerer mice was compared to normal mice by recording the number of pups produced and the number of oocytes occurring. It was found that staggerer mothers produced smaller litters than controls and the number of oocytes produced in their ovaries was reduced by the staggerer mutation. These results indicate a pleiotropic effect on fertility of the Rora(sg) gene underlying the cerebellar abnormalities of the staggerer mutant.

Animals↗
PubMed2005

Learning spatial orientation tasks in the radial-maze and structural variation in the hippocampus in inbred mice.

In the present paper we review a series of experiments showing that heritable variations in the size of the hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields correlate with performance in spatial, but not non-spatial radial-maze tasks. Experimental manipulation of the size of this projection by means of early postnatal hyperthyroidism produces the effects predicted from the correlations obtained with inbred mouse strains. Although the physiological mechanisms behind these correlations are unknown as yet, several lines of evidence indicate that these correlations are causal.

Journal Article↗
PubMed2005

Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse.

BACKGROUND: The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). RESULTS: Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. CONCLUSION: Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models.

Journal Article↗
PubMed2005

Genetic mouse models of Alzheimer's disease.

In the current minireview, we focus on genetic mouse models of Alzheimer's disease (AD). Because various excellent, up-to-date reviews, special issues, and reliable websites are already dedicated to the genetics of Alzheimer's disease in general and of animal models in particular, this review is not meant to be comprehensive. Rather, we aim to steer the Alzheimer's novice through the recent mouse literature on AD. Special attention will be paid to genetic models that have been tested behaviorally.

Alzheimer Disease↗
PubMed2004

Flanking gene and genetic background problems in genetically manipulated mice.

Mice carrying engineered genetic modifications have become an indispensable tool in the study of gene functioning. The interpretation of results obtained with targeted mutants is not completely straightforward, however, because of genetic complications due to linkage and epistasis. Effects of closely linked genes flanking the targeted locus might sometimes be responsible for phenotypic changes ascribed to the null mutation. The effects of the latter might also be modified by the general genetic background. This review presents some examples and discusses some simple strategies to deal with these complications.

5' Flanking Region↗
PubMed2004

13-cis-retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice.

The active component of the acne drug Accutane is 13-cis-retinoic acid (RA), and it is highly teratogenic for the developing central nervous system. Very little is known, however, regarding the effect of this drug on the adult brain. Regions of the brain that may be susceptible to RA are those that continue to generate new neurons. In the adult mouse, neurogenesis is maintained in the hippocampus and subventricular zone. This report demonstrates that a clinical dose (1 mg/kg/day) of 13-cis-RA in mice significantly reduces cell proliferation in the hippocampus and the subventricular zone, suppresses hippocampal neurogenesis, and severely disrupts capacity to learn a spatial radial maze task. The results demonstrate that the regions of the adult brain where cell proliferation is ongoing are highly sensitive to disruption by a clinical dose of 13-cis-RA.

Animals↗
PubMed2004

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Animals↗
PubMed2004

Genetic dissection of learning and memory in mice.

In this minireview, we discuss different strategies to dissect genetically the keystones of learning and memory. First, we broadly sketch the neurogenetic analysis of complex traits in mice. We then discuss two general strategies to find genes affecting learning and memory: candidate gene studies and whole genome searches. Next, we briefly review more recently developed techniques, such as microarrays and RNA interference. In addition, we focus on gene-environment interactions and endophenotypes. All sections are illustrated with examples from the learning and memory field, including a table summarizing the latest information about genes that have been shown to have effects on learning and memory.

Animals↗
PubMed2003

Agonistic behavior and unpredictable chronic mild stress in mice.

A significant proportion of patients suffering from major clinical depression exhibit sudden bursts of anger often described as "panic attacks without anxiety or fear" or "irritability." We investigated aggressive behavior in mice from four different inbred strains subjected to unpredictable chronic mild stress (UCMS). Our results show that UCMS affects self-grooming behavior, as evaluated by the state of an animal's fur, with severity of symptoms differing according to genetic background. Furthermore, UCMS increased aggression both in a resident-intruder test and between cage-mates. UCMS is therefore a valuable model of the problematic aggressive behavior seen in depressive patients.

Aggression↗
PubMed2003

The nature and identification of quantitative trait loci: a community's view.

This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?

Animals↗
PubMed2002

Chronic inhibition of glutamine synthetase is not associated with impairment of learning and memory in mice.

The convulsant methionine sulfoximine (MSO) is a byproduct of the agenized flour commonly used for feeding domestic animals decades ago. MSO is a powerful glycogenic and epileptogenic agent, and it is an irreversible inhibitor of glutamine synthetase. This latter effect was hypothesized to be responsible for the increase in the incidence of some neuropathologies in humans, such as Alzheimer's disease or Parkinson's disease. In order to test this hypothesis, we chronically administered MSO to two inbred strains of mice, C57BL/6J and BALB/cJ, and analyzed possible alterations in learning and memory features of these mice. Mice were given 20 mg/kg of MSO three times a week for 10 weeks. Spatial learning capabilities assessed with a radial maze were not affected by the long-term MSO treatment, although activity was significantly decreased in BALB/cJ mice. Thus, our data suggest that long-term administration of non-convulsive and non-glycogenic doses of MSO do not alter the spatial memory of mice. Our results do not support the hypothesis that chronic treatment with MSO influences hippocampus-dependent learning abilities in mice.

Animals↗
PubMed2002

Behavioral and neuroanatomical characterization of FVB/N inbred mice.

The inbred strain FVB/N is becoming increasingly popular to generate transgenic animals. We compared animals from this strain with well-characterized C57BL/6J animals on four different behavioral tests: the elevated plus maze test of anxiety, a standard opponent aggression test, the open-field test, and spatial learning in a radial maze. Our results indicate that FVB/N animals have slightly higher levels of anxiety and aggression, are hyperactive, and have a clear learning deficit. The latter finding seems to be related to an exceptionally small intrapyramidal and infrapyramidal mossy fiber projection. It is recommended that transgenic experiments employing this strain use F1 crosses between FVB/N and C57BL/6J as much as possible for behavioral experiments intended to evaluate spatial learning.

Aggression↗