Intellectual disability is a generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. The condition can result from a wide variety of genetic and environmental causes.
MK801 induced cognitive deficit
MK-801, also known as dizocilpine, is an antagonist of the NMDA glutamate receptor. It is commonly used to model cognitive impairment associated with psychosis and schizophrenia.
Sylics has extensive experience with measuring MK-801 injected mice and rats in a wide range of behavioral paradigms. These include the Morris Water Maze and our sensitive CognitionWall discrimation learning task.
Scopolamine induced cognitive deficit
Scopolamine is a naturally occurring anticholinergic drug that works by blocking the effects of acetylcholine on muscarinic receptors. This results in widespread impairments in learning, memory, and cognition.
Sylics has successfully used scopolamine to induce cognitive impairments in the CognitionWall test in the PhenoTyper in mice, and in conventional tests in both mice (Remmelink et al, 2017) and rats (Bruinsma et al 2019). In particular, we observe robust impairments in the self-paced 5-choice serial reaction time task (5CSRTT), which is the most widely used task measuring impulsive action and attention performance.
FMR1 Fragile X
Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. FXS is caused by changes in the Fmr1 gene, which encodes a protein involved in brain development.
The Fmr1 knockout mouse model is perceived as highly translational relevant due to the genetic and phenotypic similarities with patients. At Sylics, we observe abnormalities in social and cognitive behavior in an Fmr1 KO model.
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by the deletion of a small segment of chromosome 22. The disease is associated with developmental delay, learning impairments, and a 30-fold increase in the risk of developing schizophrenia.
Mice with 22q11 microdeletions are perceived as highly translational relevant due to the genetic and phenotypic similarities between the mouse model and patients. At Sylics, we have observed robust impairments in sensorimotor gating and working memory.
Bruinsma B, Terra H, de Kloet SF, Luchicchi A, Timmerman AJ, Remmelink E, Loos M, Pattij T, Mansvelder HD. An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats. Psychopharmacology (Berl). 2019 Jul;236(7):2015-2026. doi: 10.1007/s00213-019-05189-0. Epub 2019 Mar 2. PMID: 30826849; PMCID: PMC6647605. https://pubmed.ncbi.nlm.nih.gov/30826849/
Remmelink E, Chau U, Smit AB, Verhage M, Loos M. A one-week 5-choice serial reaction time task to measure impulsivity and attention in adult and adolescent mice. Sci Rep. 2017 Feb 15;7:42519. doi: 10.1038/srep42519. PMID: 28198416; PMCID: PMC5309744. https://pubmed.ncbi.nlm.nih.gov/28198416/
Keywords: ADHD, psychiatry
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