title: Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.
abstract: BACKGROUND
  Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory.
  
  
  METHODS
  To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment.
  
  
  RESULTS
  CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in (1)H-MRS.
  
  
  CONCLUSIONS
  Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that (1)H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden 01307, Dresden, Germany ; German Center for Neurodegenerative Diseases (DZNE) Dresden 10307, Dresden, Germany ; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden 01307, Dresden, Germany.
authors.forename: Moritz D
authors.initials: MD
authors.lastname: Brandt
authors.affiliation: Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
authors.forename: Kalina
authors.initials: K
authors.lastname: Brandt
authors.affiliation: Department of Neuroradiology, Technische Universität Dresden 01307, Dresden, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Werner
authors.affiliation: Institute for Psychology, University of Halle Halle, Germany.
authors.forename: Robby
authors.initials: R
authors.lastname: Schönfeld
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden 01307, Dresden, Germany ; German Center for Neurodegenerative Diseases (DZNE) Dresden 10307, Dresden, Germany ; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden 01307, Dresden, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Loewenbrück
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Dresden 10307, Dresden, Germany ; Department of Psychiatry, University Hospital Dresden 01307, Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Donix
authors.affiliation: Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.affiliation: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden 01307, Dresden, Germany ; Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Department of Neuroradiology, Technische Universität Dresden 01307, Dresden, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Kummer
authors.affiliation: Institute for Psychology, University of Halle Halle, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Leplow
authors.affiliation: Division of Neurodegenerative Diseases, Department of Neurology, Technische Universität Dresden 01307, Dresden, Germany ; German Center for Neurodegenerative Diseases (DZNE) Dresden 10307, Dresden, Germany ; Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden 01307, Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Storch
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009415:Nerve Net; D055495:Neurogenesis / Q000187:drug effects / Q000528:radiation effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010865:Pilot Projects; D065852:Spatial Memory / Q000187:drug effects / Q000528:radiation effects
keywords: Adult neurogenesis; choline; human; proton magnetic resonance spectroscopy; virtual water maze