Neurodevelopmental and psychiatric disorders

Psychiatric or mental disorders are umbrella terms for behavioral or mental patterns that cause significant functional impairment and distress. These disorders are often at least in part the result of neurodevelopmental problems.

Schizophrenia

Schizophrenia is characterized by psychotic symptoms, such as hallucinations, delusions, paranoia, and disorganized thinking. Other symptoms include cognitive impairments, apathy, social withdrawal, and decreased emotional expression.

Sylics offers services with several induced and genetic models of schizophrenia. Depending on the model, these show deficits in distinct behavioral domains relevant to Schizophrenia including deficits in learning in the CognitionWall test, working memory in the 8-arm radial maze and the highly translation sensorimotor gating test (PPI test). The 22q11 mouse model is perceived as highly translational relevant due to the genetic and phenotypic similarities between the mouse model and patients.

The auditory pre-pulse inhibition (PPI) test is a highly translational test for sensorimotor gating in humans and rodents.
In the three chamber test for social interaction, WT mice spent more time in the compartment that contained a novel stimulus mouse in comparison with the object compartment. In contrast to WT mice, Fmrp1 KO did not show a preference for social interaction.

Autism spectrum disorders

Patients with autism spectrum disorders have difficulties with social behavior and may also display restricted, repetitive patterns of behavior, interests, or activities. A variety of neurodevelopmental conditions are associated with autism.

Sylics offers a variety of mouse models with genetic alterations related to autism, such as the Fmr1 knock out mouse model of Fragile-X syndrome. Similar to humans with Fragile-X syndrome, mouse models of autism show profound alterations in social behavior, activity and cognition. In addition to this model, Sylics has characterized the behavior of several other mouse lines with relevance to autism, please contact us for more information.

Depression

Major depressive disorder (MDD) or depression is characterized by at persistent low mood, social withdrawal, inability to experience pleasure (anhedonia), cognitive impairment, anxiety, and low energy. It is thought that genetic, developmental, immune, stress, social, and environmental factors play a role in depression.

Several factors can induce changes in brain and behavior that mimic that mimic aspects of MDD, including early life stress and social defeat. In particular the social defeat model in rats leads to altered cognition, social behavior and anxiety and is responsive to currently prescribed antidepressants.

When a bright LightSpot was switched on during the dark phase in the PhenoTyper cage, control treated mice spent less time outside of the shelter. This anxiety phenotype could be reversed with the golden-standard anxiolytic drug diazepam.

Anxiety and post traumatic stress disorder

Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety, panic, and/or fear. Post-traumatic stress disorder (PTSD) is one such disorder, where people have persistent flashbacks to a traumatic event.

In contrast to many other diseases, anxiety can be modeled in wild-type mice using a variety of behavior paradigms. Sylics offers a wide range of both conventional and automated behavioral tests to study anxiety phenotypes in mice. For example our in-house developed LightSpot test measures anxiety in mice, which could be rescued with the anxiolytic drug diazepam.

DiGeorge syndrome - 22q11.2 deletion

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion in the 22q11.2 locus on human Chromosome 22. Symptoms vary, but often include intellectual disability and psychiatric disorders. It causes a 20-fold increased risk of schizophrenia. At Sylics, using our own tests and protocols, we have validated the presence of relevant behavioral changes in a 22q11 model originally developed by a research team headed by Dr. M. Didriksen at Lundbeck A/S [LINK]. For instance, mice carrying the 22q11 deletion show a robust deficit in sensorimotor gating measured as the percentage of prepulse inhibition (PPI) of a startle response. Furthermore, we detected significant deficits in working memory performance in terms of re-entry errors in the 8-arm radial maze.

Heterozygous deletion of genes residing in the human 22q11 chromosomal region leads to a robust deficit in sensorimotor gating in comparison with control litter mates. In line with previous publications, we detected deficits in working memory in the 8-arm radial maze in 22q11 mutants.

More information

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