TY - JOUR
T1 - The expression of the distal dystrophin isoforms Dp140 and Dp71 in the human epileptic hippocampus in relation to cognitive functioning
AU - Hoogland, Govert
AU - Hendriksen, Ruben G. F.
AU - Slegers, Rutger J.
AU - Hendriks, Marc P. H.
AU - Schijns, Olaf E. M. G.
AU - Aalbers, Marlien W.
AU - Vles, Johan S. H.
N1 - Funding Information:
The authors would like to thank Dr. Jim Dings, neurosurgeon from Maastricht University Medical Centre, for the surgical resection of the specimens.
Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/2
Y1 - 2019/2
N2 - Dystrophin is an important protein within the central nervous system. The absence of dystrophin, characterizing Duchenne muscular dystrophy (DMD), is associated with brain related comorbidities such as neurodevelopmental (e.g., cognitive and behavioural) deficits and epilepsy. Especially mutations in the downstream part of the DMD gene affecting the dystrophin isoforms Dp140 and Dp71 are found to be associated with cognitive deficits. However, the function of Dp140 is currently not well understood and its expression pattern has previously been implicated to be developmentally regulated. Therefore, we evaluated Dp140 and Dp71 expression in human hippocampi in relation to cognitive functioning in patients with drug-resistant temporal lobe epilepsy (TLE) and post-mortem controls. Hippocampal samples obtained as part of epilepsy surgery were quantitatively analyzed by Western blot and correlations with neuropsychological test results (i.e., memory and intelligence) were examined. First, we demonstrated that the expression of Dp140 does not appear to differ across different ages throughout adulthood. Second, we identified an inverse correlation between memory loss (i.e., verbal and visual memory), but not intelligence (i.e., neither verbal nor performance), and hippocampal Dp140 expression. Finally, patients with TLE appeared to have similar Dp140 expression levels compared to post-mortem controls without neurological disease. Dp140 may thus have a function in normal cognitive (i.e., episodic memory) processes.
AB - Dystrophin is an important protein within the central nervous system. The absence of dystrophin, characterizing Duchenne muscular dystrophy (DMD), is associated with brain related comorbidities such as neurodevelopmental (e.g., cognitive and behavioural) deficits and epilepsy. Especially mutations in the downstream part of the DMD gene affecting the dystrophin isoforms Dp140 and Dp71 are found to be associated with cognitive deficits. However, the function of Dp140 is currently not well understood and its expression pattern has previously been implicated to be developmentally regulated. Therefore, we evaluated Dp140 and Dp71 expression in human hippocampi in relation to cognitive functioning in patients with drug-resistant temporal lobe epilepsy (TLE) and post-mortem controls. Hippocampal samples obtained as part of epilepsy surgery were quantitatively analyzed by Western blot and correlations with neuropsychological test results (i.e., memory and intelligence) were examined. First, we demonstrated that the expression of Dp140 does not appear to differ across different ages throughout adulthood. Second, we identified an inverse correlation between memory loss (i.e., verbal and visual memory), but not intelligence (i.e., neither verbal nor performance), and hippocampal Dp140 expression. Finally, patients with TLE appeared to have similar Dp140 expression levels compared to post-mortem controls without neurological disease. Dp140 may thus have a function in normal cognitive (i.e., episodic memory) processes.
KW - Duchenne muscular dystrophy, hippocampal sclerosis, intelligence, memory, temporal lobe epilepsy
KW - DUCHENNE MUSCULAR-DYSTROPHY
KW - WECHSLER MEMORY SCALE
KW - INTELLECTUAL IMPAIRMENT
KW - GLYCOPROTEIN COMPLEX
KW - BRAIN DYSTROPHIN
KW - WESTERN-BLOT
KW - TASK-FORCE
KW - QUANTIFICATION
KW - DELETIONS
KW - SYSTEM
U2 - 10.1002/hipo.23015
DO - 10.1002/hipo.23015
M3 - Article
C2 - 30069964
SN - 1050-9631
VL - 29
SP - 102
EP - 110
JO - Hippocampus
JF - Hippocampus
IS - 2
ER -