Learning, memory and blood–brain barrier pathology in Duchenne muscular dystrophy mice lacking Dp427, or Dp427 and Dp140

• Published in: Genes, brain and behavior Vol. 23; no. 3; pp. e12895 - n/a
• Main Authors: Verhaeg, Minou, Adamzek, Kevin, Vijver, Davy, Putker, Kayleigh, Engelbeen, Sarah, Wijnbergen, Daphne, Overzier, Maurice, Suidgeest, Ernst, Weerd, Louise, Aartsma‐Rus, Annemieke, Putten, Maaike
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2024; John Wiley & Sons, Inc
• Subjects: Animals; Aquaporin 4; Aquaporin 4 - genetics; Aquaporin 4 - metabolism; Behavior; Blood-brain barrier; Blood-Brain Barrier - metabolism; cognition; Duchenne's muscular dystrophy; Dystrophin; Dystrophin - genetics; Dystrophin - metabolism; Glial fibrillary acidic protein; Isoforms; Male; Memory; Memory, Short-Term; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscular dystrophy; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - metabolism; Muscular Dystrophy, Duchenne - physiopathology; neuromuscular disease; Original; Spatial discrimination learning; spatial learning; Spatial memory; spontaneous behavior; spontaneous behavior; neuromuscular disease; spatial learning; dystrophin; cognition
• ISSN: 1601-1848; 1601-183X; 1601-183X
• DOI: 10.1111/gbb.12895

Duchenne muscular dystrophy is a severe neuromuscular disorder that is caused by mutations in the DMD gene, resulting in a disruption of dystrophin production. Next to dystrophin expression in the muscle, different isoforms of the protein are also expressed in the brain and lack of these isoforms leads to cognitive and behavioral deficits in patients. It remains unclear how the loss of the shorter dystrophin isoform Dp140 affects these processes. Using a variety of behavioral tests, we found that mdx and mdx4cv mice (which lack Dp427 or Dp427 + Dp140, respectively) exhibit similar deficits in working memory, movement patterns and blood–brain barrier integrity. Neither model showed deficits in spatial learning and memory, learning flexibility, anxiety or spontaneous behavior, nor did we observe differences in aquaporin 4 and glial fibrillary acidic protein. These results indicate that in contrast to Dp427, Dp140 does not play a crucial role in processes of learning, memory and spontaneous behavior. This study shows that mice lacking Dp427 or Dp427 + Dp140 exhibit similar deficits in memory, activity and blood brain barrier integrity, while aquaporin 4 and glial fibrillary acidic protein expression remain unaffected. These results indicate that in contrast to Dp427, Dp140 does not play a crucial role in processes of learning, memory and spontaneous behavior.