Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.
Moritz D Brandt, Kalina Brandt, Annett Werner, Robby Schönfeld, Kai Loewenbrück, Markus Donix, Markus Schaich, Martin Bornhäuser, Rüdiger von Kummer, Bernd Leplow, Alexander Storch
Author Information
Moritz D Brandt: 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.
Kalina Brandt: Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
Annett Werner: Department of Neuroradiology, Technische Universität Dresden 01307, Dresden, Germany.
Robby Schönfeld: Institute for Psychology, University of Halle Halle, Germany.
Kai Loewenbrück: 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.
Markus Donix: German Center for Neurodegenerative Diseases (DZNE) Dresden 10307, Dresden, Germany ; Department of Psychiatry, University Hospital Dresden 01307, Dresden, Germany.
Markus Schaich: Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
Martin Bornhäuser: Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden 01307, Dresden, Germany ; Department of Haematology and Oncology, University Hospital Dresden 01307, Dresden, Germany.
Rüdiger von Kummer: Department of Neuroradiology, Technische Universität Dresden 01307, Dresden, Germany.
Bernd Leplow: Institute for Psychology, University of Halle Halle, Germany.
Alexander Storch: 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.
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. CONCLUSION: 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.
