The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

Introduction: Social deprivation during early life can severely affect mental health later in adulthood, leading to the development of behavioural traits associated with several major psychiatric disorders including schizophrenia. This has led to the application of social isolation in laboratory animals to model the impact of environmental factors on the aetiopathology of schizophrenia. However, controversy exists over the precise behavioural profile and the robustness of some of the reported effects of social isolation rearing. Materials and methods: Here, we evaluated the efficacy of postweaning social isolation to induce schizophrenia-related behavioural deficits in C57BL/6 mice of both sexes. Results: The effects of social isolation clearly differed between sexes: isolated male but not female mice exhibited multiple habituation deficits and enhanced locomotor reaction to amphetamine. Discussion: The preferential vulnerability in the male sex corresponds well with the earlier disease onset and poorer prognosis in male relative to female schizophrenic patients. In contrast, we observed no evidence for a disruption of sensorimotor gating in the prepulse inhibition paradigm despite the efficacy of social isolation to alter startle reactivity. With both success and failure in the induction of schizophrenia-related endophenotypes, the present study thus provides important characterizations and qualifications to the application of the social isolation model in mice. Conclusions: We conclude that social isolation in mice represents a valuable tool for the examination of candidate genes within the context of the "two-hit” hypothesis of the aetiological processes in schizophreni

The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex

ISSN:0033-3158ISSN:1432-207

Mouse and rat ultrasonic vocalizations in neuroscience and neuropharmacology: State of the art and future applications

Mice and rats emit ultrasonic vocalizations (USVs), which may express their arousal and emotional states, to communicate with each other. There is continued scientific effort to better understand the functions of USVs as a central element of the rodent behavioral repertoire. However, studying USVs is not only important because of their ethological relevance, but also because they are widely applied as a behavioral readout in various fields of biomedical research. In mice and rats, a large number of experimental models of brain disorders exist and studying the emission of USVs in these models can provide valuable information about the health status of the animals and the effectiveness of possible interventions, both environmental and pharmacological. This review (i) provides an updated overview of the contexts in which ultrasonic calling behaviour of mice and rats has particularly high translational value, and (ii) gives some examples of novel approaches and tools used for the analysis of USVs in mice and rats, combining qualitative and quantitative methods. The relevance of age and sex differences as well as the importance of longitudinal evaluations of calling and non-calling behaviour is also discussed. Finally, the importance of assessing the communicative impact of USVs in the receiver, that is, through playback studies, is highlighted

Environmental enrichment eliminates the anxiety phenotypes in a triple transgenic mouse model of Alzheimer's disease

Although the impacts of environmental enrichment (EE) in several genetic models of Alzheimer's disease (AD) have been documented, the focus has remained predominantly on cognition. Few have investigated the expression of emotional phenotypes that mimic the notable affective features in AD. Here, we studied the interaction between EE and the coexpression of three genetic risk factors (mutations) for AD. In a longitudinal design, 3×Tg-AD mutants and wild type controls were compared at 6-7 months and subsequently at 12-13 months of age. Under standard housing, phenotypes of heightened anxiety levels were identified in the 3×Tg-AD mice in the elevated plus maze and open-field tests. Such trait differences between genotypes were substantially diminished under EE housing, which was attributable to the anxiolytic impact of EE on the mutant mice as much as the anxiogenic impact of EE on the wild type mice. In contrast, the phenotypes in learned fear were not significantly modified by EE in the tests of Pavlovian freezing and conditioned active avoidance conducted at either age. Rearing under EE thus has uncovered a novel distinction between innate and acquired expressions of fear response in the 3×Tg-AD mouse model that might be relevant to the mental health management of AD

Gene-Environment Interactions in Neurodevelopmental Disorders

ISSN:2090-5904ISSN:1687-544

Cells

Phytocannabinoids, including the non-addictive cannabis component cannabidivarin (CBDV), have been reported to hold therapeutic potential in several neurodevelopmental disorders (NDDs). Nonetheless, the therapeutic value of phytocannabinoids for treating Fragile X syndrome (FXS), a major NDD, remains unexplored. Here, we characterized the neurobehavioral effects of CBDV at doses of 20 or 100 mg/kg in the Fmr1-knockout (Fmr1-KO) mouse model of FXS using two temporally different intraperitoneal regimens: subchronic 10-day delivery during adulthood (Study 1: rescue treatment) or chronic 5-week delivery at adolescence (Study 2: preventive treatment). Behavioral tests assessing FXS-like abnormalities included anxiety, locomotor, cognitive, social and sensory alterations. Expression of inflammatory and plasticity markers was investigated in the hippocampus and prefrontal cortex. When administered during adulthood (Study 1), the effects of CBDV were marginal, rescuing at the lower dose only the acoustic hyper-responsiveness of Fmr1-KO mice and at both doses their altered hippocampal expression of neurotrophins. When administered during adolescence (Study 2), CBDV at both doses prevented the cognitive, social and acoustic alterations of adult Fmr1-KO mice and modified the expression of several inflammatory brain markers in both wild-type littermates and mutants. These findings warrant the therapeutic potential of CBDV for preventing neurobehavioral alterations associated with FXS, highlighting the relevance of its early administration.Bordeaux Region Aquitaine Initiative for Neuroscienc

Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule.

International audienc

Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

International audienc