Article

Translational neuroscience of schizophrenia: seeking a meeting of minds between mouse and man.

Department of Neuroscience and Pharmacology, University Medical Center Utrecht, 3584CG Utrecht, The Netherlands.
Science translational medicine (Impact Factor: 14.41). 09/2011; 3(102):102mr3. DOI: 10.1126/scitranslmed.3002917
Source: PubMed

ABSTRACT Understanding the etiology of developmental brain disorders such as schizophrenia is critical for achieving advances in treatment and requires new research strategies that control for individual variation in genetic background, environmental challenges, and expression of phenotype. SYSGENET, a European systems genetics network for the study of complex genetic human diseases with mouse genetic reference populations, brought together in Helsinki a cross-disciplinary group of clinical and basic scientists and mouse geneticists to debate, formulate, and prioritize a strategy for future research based on mouse models. The main conclusions of this meeting are summarized here.

0 Bookmarks
 · 
161 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutant mice play an increasingly important role in understanding disease processes at multiple levels. In particular, they illuminate the impact of risk genes for disease on such processes. This article reviews recent advances in the application of mutant mice to study the intricacies of dopaminergic (DAergic) function in relation to the putative pathophysiology of psychotic illness, particularly schizophrenia, and antipsychotic drug action. It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1, their interactions with environmental factors, and with each other (epistasis). In overview, it considers new schemas for understanding psychotic illness that integrate DAergic pathophysiology with developmental, social, and cognitive processes, and how mutant mouse models can reflect and inform on such schemas.
    Progress in brain research 01/2014; 211:79-112. DOI:10.1016/B978-0-444-63425-2.00004-0 · 4.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6 J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129 Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10–12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129 Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2014; DOI:10.1016/j.euroneuro.2014.01.013 · 3.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Animal studies play a central role in the identification and testing of novel drugs for CNS disorders. In his longstanding career, Berend Olivier has significantly contributed to CNS drug discovery by applying and supporting novel views and methodologies in the fields of behavioural neuroscience, pharmacology, and (epi-) genetics. Here we review and put forward some of these integrated approaches that have led to a productive collaboration and new insights into the genetic and epigenetic regulation of neurobehavioural traits related to psychiatric disorders.

Full-text

Download
64 Downloads
Available from
May 28, 2014