Translational Neuroscience of Schizophrenia: Seeking a Meeting of Minds Between Mouse and Man

Kas, Martien; Kahn, René S.; Collier, David; Waddington, John L.; Ekelund, Jesper; Porteous, David J.; Schughart, Klaus; Hovatta, Iiris

doi:10.1126/scitranslmed.3002917

Cited by 18 publications

(9 citation statements)

References 64 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hippocampal slices (350-400 µM) were cut with a vibratome. The slices were superfused with artificial cerebrospinal fluid (ACSF) 2 , at a rate of 1-2 mL/min (32°C). Whole-cell recordings were obtained from CA1 pyramidal neurons with pipettes with tip resistance of 3-4 MΩ and currents were recorded with MultiClamp 700A amplifier (Molecular Devices, Inc) and were sampled at 12.5 kHz.…”

Section: Electrophysiologymentioning

confidence: 99%

“…1 A critical challenge in schizophrenia research is to create animal models to illuminate the underlying pathophysiology and to develop new treatments. 2 Modeling psychiatric disorders in animals is obviously challenging. 3 However, several characteristics of schizophrenia have correlates in mice such as abnormal social behavior, impaired working memory, and defective prepulse inhibition (PPI).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes

Peltola

Kuja-Panula

Liuhanen

et al. 2015

SCHBUL

View full text Add to dashboard Cite

The enormous variability in electrical properties of neurons is largely affected by a multitude of potassium channel subunits. Kv2.1 is a widely expressed voltage-dependent potassium channel and an important regulator of neuronal excitability. The Kv2.1 auxiliary subunit AMIGO constitutes an integral part of the Kv2.1 channel complex in brain and regulates the activity of the channel. AMIGO and Kv2.1 localize to the distinct somatodendritic clusters at the neuronal plasma membrane. Here we have created and characterized a mouse line lacking the AMIGO gene. Absence of AMIGO clearly reduced the amount of the Kv2.1 channel protein in mouse brain and altered the electrophysiological properties of neurons. These changes were accompanied by behavioral and pharmacological abnormalities reminiscent of those identified in schizophrenia. Concomitantly, we have detected an association of a rare, population-specific polymorphism of KV2.1 (KCNB1) with human schizophrenia in a genetic isolate enriched with schizophrenia. Our study demonstrates the involvement of AMIGO-Kv2.1 channel complex in schizophrenia-related behavioral domains in mice and identifies KV2.1 (KCNB1) as a strong susceptibility gene for schizophrenia spectrum disorders in humans.

show abstract

Section: Electrophysiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes

Peltola

Kuja-Panula

Liuhanen

et al. 2015

SCHBUL

View full text Add to dashboard Cite

show abstract

“…Some of these considerations have encouraged animal researchers to develop translational models that incorporate multiple etiologically relevant risk factors (Ayhan et al 2009 ;Kas et al 2011 ). On the basis of the role of prenatal infection in schizophrenia, there have been recent attempts to explore the cumulative impact of immune-related environmental challenges and distinct genetic abnormalities in the disruption of brain and behavioral development.…”

Section: The Future: Deconstructing the Phenotypes And Broadening Thementioning

confidence: 99%

Developmental Immune Activation Models with Relevance to Schizophrenia

Meyer

2015

Current Topics in Neurotoxicity

View full text Add to dashboard Cite

It is increasingly appreciated that altered neuroimmune mechanisms might play a role in the development of schizophrenia and related psychotic illnesses. On the basis of human epidemiological fi ndings, a number of translational rodent models have been established to explore the consequences of prenatal immune activation on brain and behavioral development. The currently existing models are based on maternal gestational exposure to human infl uenza virus, the viral mimic polyriboinosinic-polyribocytidilic acid [Poly(I:C)], the bacterial endotoxin lipopolysaccharide, the locally acting infl ammatory agent turpentine, or selected infl ammatory cytokines. These models are pivotal for establishing causal relationships and for identifying cellular and molecular mechanisms that affect normal brain development in the event of early-life immune exposures. An important aspect of developmental immune activation models is that they allow a multifaceted, longitudinal monitoring of the disease process as it unfolds during the course of neurodevelopment from prenatal to adult stages of life. An important recent refi nement of these models is the incorporation of multiple etiologically relevant risk factors by combining prenatal immune challenges with specifi c genetic manipulations or additional environmental adversities. Converging fi ndings from such recent experimental attempts suggest that prenatal infection can act as a "neurodevelopmental disease primer" that is likely relevant for a number of chronic mental illnesses. Hence, the adverse effects induced by prenatal infection might refl ect an early entry into the neuropsychiatric route, but the specifi city of subsequent disease or symptoms is likely to be strongly infl uenced by the genetic and environmental context in which the prenatal infectious process occurs.

show abstract

“…However, many behaviours affected in disease states can be identified as equivalent in humans and model species at the level of the endophenotype, such as anxiety, arousal, cognition and social interaction. An ethological approach to identifying and assessing these basic behavioural building blocks is beginning to bear fruit (Gould and Gottesman 2006;Kas et al 2007Kas et al , 2011a. For example in modelling schizophrenia, anhedonia, asociality and avolition are at least theoretically accessible through behavioural assays in both humans and animals (Kas et al 2011a) and characteristics of autistic spectrum disorders, for example insistence on routine and resistance to change in tasks that involve reversal learning or set shifting, high anxiety and low socialization can be all assessed in mouse models (Bishop and Lahvis 2011;Amodeo et al 2012;Moy et al 2007;Naviaux et al 2014;Nestler and Hyman 2010).…”

Section: Phenotypes Endophenotypes and Operationalisationsmentioning

confidence: 99%

Best behaviour? Ontologies and the formal description of animal behaviour

et al. 2015

View full text Add to dashboard Cite

The development of ontologies for describing animal behaviour has proved to be one of the most difficult of all scientific knowledge domains. Ranging from neurological processes to human emotions, the range and scope needed for such ontologies is highly challenging, but if data integration and computational tools such as automated reasoning are to be fully applied in this important area the underlying principles of these ontologies need to be better established and development needs detailed coordination. Whilst the state of scientific knowledge is always paramount in ontology and formal description framework design, this is a particular problem with neurobehavioural ontologies where our understanding of the relationship between behaviour and its underlying biophysical basis is currently in its infancy. In this commentary, we discuss some of the fundamental problems in designing and using behaviour ontologies, and present some of the best developed tools in this domain.

show abstract

Translational Neuroscience of Schizophrenia: Seeking a Meeting of Minds Between Mouse and Man

Cited by 18 publications

References 64 publications

AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes

AMIGO-Kv2.1 Potassium Channel Complex is Associated With Schizophrenia-Related Phenotypes

Developmental Immune Activation Models with Relevance to Schizophrenia

Best behaviour? Ontologies and the formal description of animal behaviour

Contact Info

Product

Resources

About