title: Genetic and pharmacological intervention of the p75NTR pathway alters morphological and behavioural recovery following traumatic brain injury in mice.
abstract: OBJECTIVE
  Neurotrophin levels are elevated after TBI, yet there is minimal regeneration. It was hypothesized that the pro-neurotrophin/p75NTR pathway is induced more than the mature neurotrophin/Trk pathway and that interfering with p75 signalling improves recovery following TBI.
  
  
  METHODS
  Lateral Fluid Percussion (LFP) injury was performed on wildtype and p75 mutant mice. In addition, TrkB agonist 7,8 Dihydroxyflavone or p75 antagonist TAT-Pep5 were tested. Western blot and immunohistochemistry revealed biochemical and cellular changes. Morris Water Maze and Rotarod tests demonstrated cognitive and vestibulomotor function.
  
  
  RESULTS
  p75 was up-regulated and TrkB was down-regulated 1 day post-LFP. p75 mutant mice as well as mice treated with the p75 antagonist or the TrkB agonist exhibited reduced neuronal death and degeneration and less astrocytosis. The cells undergoing apoptosis appear to be neurons rather than glia. There was improved motor function and spatial learning in p75 mutant mice and mice treated with the p75 antagonist.
  
  
  CONCLUSIONS
  Many of the pathological and behavioural consequences of TBI might be due to activation of the pro-neurotrophin/p75 toxic pathway overriding the protective mechanisms of the mature neurotrophin/Trk pathway. Targeting p75 can be a novel strategy to counteract the damaging effects of TBI.
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Alder
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Fujioka
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Giarratana
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Wissocki
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Keya
authors.initials: K
authors.lastname: Thakkar
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Phung
authors.initials: P
authors.lastname: Vuong
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Bijal
authors.initials: B
authors.lastname: Patel
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Trisha
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Rami
authors.initials: R
authors.lastname: Elsabeh
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Ankit
authors.initials: A
authors.lastname: Parikh
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Hartaj S
authors.initials: HS
authors.lastname: Girn
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: David
authors.initials: D
authors.lastname: Crockett
authors.affiliation: a Rutgers Robert Wood Johnson Medical School , Piscataway , NJ , USA.
authors.forename: Smita
authors.initials: S
authors.lastname: Thakker-Varia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D047309:Flavones / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000378:metabolism; D020813:Receptor, trkB / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C485383:6,7-dihydroxyflavone; D019208:Brain-Derived Neurotrophic Factor; D047309:Flavones; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020813:Receptor, trkB
keywords: Animal models; learning and memory; locomotor function; neurotrophic factors