title: Site-specific and time-dependent activation of the endocannabinoid system after transection of long-range projections.
abstract: BACKGROUND
  After focal neuronal injury the endocannabinioid system becomes activated and protects or harms neurons depending on cannabinoid derivates and receptor subtypes. Endocannabinoids (eCBs) play a central role in controlling local responses and influencing neural plasticity and survival. However, little is known about the functional relevance of eCBs in long-range projection damage as observed in stroke or spinal cord injury (SCI).
  
  
  METHODS
  In rat organotypic entorhino-hippocampal slice cultures (OHSC) as a relevant and suitable model for investigating projection fibers in the CNS we performed perforant pathway transection (PPT) and subsequently analyzed the spatial and temporal dynamics of eCB levels. This approach allows proper distinction of responses in originating neurons (entorhinal cortex), areas of deafferentiation/anterograde axonal degeneration (dentate gyrus) and putative changes in more distant but synaptically connected subfields (cornu ammonis (CA) 1 region).
  
  
  RESULTS
  Using LC-MS/MS, we measured a strong increase in arachidonoylethanolamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) levels in the denervation zone (dentate gyrus) 24 hours post lesion (hpl), whereas entorhinal cortex and CA1 region exhibited little if any changes. NAPE-PLD, responsible for biosynthesis of eCBs, was increased early, whereas FAAH, a catabolizing enzyme, was up-regulated 48hpl.
  
  
  CONCLUSIONS
  Neuronal damage as assessed by transection of long-range projections apparently provides a strong time-dependent and area-confined signal for de novo synthesis of eCB, presumably to restrict neuronal damage. The present data underlines the importance of activation of the eCB system in CNS pathologies and identifies a novel site-specific intrinsic regulation of eCBs after long-range projection damage.
authors.affiliation: Institute for Anatomy, Leipzig University, Leipzig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kallendrusch
authors.forename: Constance
authors.initials: C
authors.lastname: Hobusch
authors.forename: Angela
authors.initials: A
authors.lastname: Ehrlich
authors.forename: Simone
authors.initials: S
authors.lastname: Ziebell
authors.forename: Natsuo
authors.initials: N
authors.lastname: Ueda
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Marco
authors.initials: M
authors.lastname: Koch
authors.forename: Faramarz
authors.initials: F
authors.lastname: Dehghani
mesh_terms: D000818:Animals; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D016923:Cell Death; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D063388:Endocannabinoids; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids