Cognitive flexibility deficits in a mouse model for the absence of full‐length dystrophin. (5th July 2016)

• Record Type: Journal Article
• Authors: Remmelink, E.; Aartsma‐Rus, A.; Smit, A. B.; Verhage, M.; Loos, M.; van Putten, M.
• Is Part Of: Genes, brain, and behavior. Volume 15:Number 6(2016)
• Page Start: 558
• Page End: 567
• Publication Date: 2016-07-05
• Subjects: Anxiety -- automated home‐cage -- cognition -- cognitive flexibility -- Duchenne muscular dystrophy -- mdx -- mouse model -- reversal learning; Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12301
• Languages: English
• ISSNs: 1601-1848

Abstract

Abstract : Duchenne muscular dystrophy (DMD) is a progressive muscle‐wasting disorder, caused by mutations in the DMD gene and the resulting lack of dystrophin. The DMD gene has seven promoters, giving rise to multiple full‐length and shorter isoforms. Besides the expression of dystrophin in muscles, the majority of dystrophin isoforms is expressed in brain and dystrophinopathy can lead to cognitive deficits, including intellectual impairments and deficits in executive function. In contrast to the muscle pathology, the impact of the lack of dystrophin on the brain is not very well studied. Here, we study the behavioral consequences of a lack of full‐length dystrophin isoforms in mdx mice, particularly with regard to domains of executive functions and anxiety. We observed a deficit in cognitive flexibility in mdx mice in the absence of motor dysfunction or general learning impairments using two independent behavioral tests. In addition, increased anxiety was observed, but its expression depended on the context. Overall, these results suggest that the absence of full‐length dystrophin in mice has specific behavioral effects that compare well to deficits observed in DMD patients. Abstract : Cognitive inflexibility and anxiety in mdx mice in the absence of motor dysfunction or general learning impairments.