title: Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy.
abstract: OBJECTIVE
  Adenosine kinase (ADK) represents the key metabolic enzyme for the regulation of extracellular adenosine levels in the brain. In adult brain, ADK is primarily present in astrocytes. Several lines of experimental evidence support a critical role of ADK in different types of brain injury associated with astrogliosis, which is also a prominent morphologic feature of temporal lobe epilepsy (TLE). We hypothesized that dysregulation of ADK is an ubiquitous pathologic hallmark of TLE.
  
  
  METHODS
  Using immunocytochemistry and Western blot analysis, we investigated ADK protein expression in a rat model of TLE during epileptogenesis and the chronic epileptic phase and compared those findings with tissue resected from TLE patients with mesial temporal sclerosis (MTS).
  
  
  RESULTS
  In rat control hippocampus and cortex, a low baseline expression of ADK was found with mainly nuclear localization. One week after the electrical induction of status epilepticus (SE), prominent up-regulation of ADK became evident in astrocytes with a characteristic cytoplasmic localization. This increase in ADK persisted at least for 3-4 months after SE in rats developing a progressive form of epilepsy. In line with the findings from the rat model, expression of astrocytic ADK was also found to be increased in the hippocampus and temporal cortex of patients with TLE. In addition, in vitro experiments in human astrocyte cultures showed that ADK expression was increased by several proinflammatory molecules (interleukin-1β and lipopolysaccharide).
  
  
  CONCLUSIONS
  These results suggest that dysregulation of ADK in astrocytes is a common pathologic hallmark of TLE. Moreover, in vitro data suggest the existence of an additional layer of modulatory crosstalk between the astrocyte-based adenosine cycle and inflammation. Whether this interaction also can play a role in vivo needs to be further investigated.
authors.affiliation: Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. e.aronica@amc.uva.nl
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zurolo
authors.forename: Anand
authors.initials: A
authors.lastname: Iyer
authors.forename: Marjolein
authors.initials: M
authors.lastname: de Groot
authors.forename: Jasper
authors.initials: J
authors.lastname: Anink
authors.forename: Caterina
authors.initials: C
authors.lastname: Carbonell
authors.forename: Erwin A
authors.initials: EA
authors.lastname: van Vliet
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Baayen
authors.forename: Detlev
authors.initials: D
authors.lastname: Boison
authors.forename: Jan A
authors.initials: JA
authors.lastname: Gorter
mesh_terms: D000248:Adenosine Kinase / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology*; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013702:Temporal Lobe / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000248:Adenosine Kinase