title: Dystrophin Distribution and Expression in Human and Experimental Temporal Lobe Epilepsy.
abstract: OBJECTIVE
  Dystrophin is part of a protein complex that connects the cytoskeleton to the extracellular matrix. In addition to its role in muscle tissue, it functions as an anchoring protein within the central nervous system such as in hippocampus and cerebellum. Its presence in the latter regions is illustrated by the cognitive problems seen in Duchenne Muscular Dystrophy (DMD). Since epilepsy is also supposed to constitute a comorbidity of DMD, it is hypothesized that dystrophin plays a role in neuronal excitability. Here, we aimed to study brain dystrophin distribution and expression in both, human and experimental temporal lobe epilepsy (TLE).
  
  
  METHODS
  Regional and cellular dystrophin distribution was evaluated in both human and rat hippocampi and in rat cerebellar tissue by immunofluorescent colocalization with neuronal (NeuN and calbindin) and glial (GFAP) markers. In addition, hippocampal dystrophin levels were estimated by Western blot analysis in biopsies from TLE patients, post-mortem controls, amygdala kindled (AK)-, and control rats.
  
  
  RESULTS
  Dystrophin was expressed in all hippocampal pyramidal subfields and in the molecular-, Purkinje-, and granular cell layer of the cerebellum. In these regions it colocalized with GFAP, suggesting expression in astrocytes such as Bergmann glia (BG) and velate protoplasmic astrocytes. In rat hippocampus and cerebellum there were neither differences in dystrophin positive cell types, nor in the regional dystrophin distribution between AK and control animals. Quantitatively, hippocampal full-length dystrophin (Dp427) levels were about 60% higher in human TLE patients than in post-mortem controls (p < 0.05), whereas the level of the shorter Dp71 isoform did not differ. In contrast, AK animals showed similar dystrophin levels as controls.
  
  
  CONCLUSIONS
  Dystrophin is ubiquitously expressed by astrocytes in the human and rat hippocampus and in the rat cerebellum. Hippocampal full-length dystrophin (Dp427) levels are upregulated in human TLE, but not in AK rats, possibly indicating a compensatory mechanism in the chronic epileptic human brain.
authors.affiliation: Department of Neurology, Maastricht University Medical Centre Maastricht, Netherlands.
authors.forename: Ruben G F
authors.initials: RG
authors.lastname: Hendriksen
authors.affiliation: Department of Neurology, Maastricht University Medical CentreMaastricht, Netherlands; School for Mental Health and Neuroscience, Maastricht UniversityMaastricht, Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schipper
authors.affiliation: School for Mental Health and Neuroscience, Maastricht UniversityMaastricht, Netherlands; Department of Neurosurgery, Maastricht University Medical CentreMaastricht, Netherlands.
authors.forename: Govert
authors.initials: G
authors.lastname: Hoogland
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Centre Maastricht, Netherlands.
authors.forename: Olaf E M G
authors.initials: OE
authors.lastname: Schijns
authors.affiliation: Department of Neurosurgery, Maastricht University Medical Centre Maastricht, Netherlands.
authors.forename: Jim T A
authors.initials: JT
authors.lastname: Dings
authors.affiliation: Department of Neurosurgery, Groningen University Medical Centre Groningen, Netherlands.
authors.forename: Marlien W
authors.initials: MW
authors.lastname: Aalbers
authors.affiliation: Department of Neurology, Maastricht University Medical Centre Maastricht, Netherlands.
authors.forename: Johan S H
authors.initials: JS
authors.lastname: Vles
keywords: Duchenne muscular dystrophy; dystrophin; epilepsy; kindling; seizures