Effects of Acute Lymphoblastic Leukemia Treatments on Cognitive Function and Hippocampal Physiology

摘要

Acute lymphoblastic leukemia (ALL) is the most common malignancy among pediatric cancer patients, accounting for over 20% of cases. ALL survivorship has reached over 80% in recent years. Cognitive decline has been implicated in side effects of ALL treatment. Our purpose was to assess the effects of intrathecal methotrexate (MTX) and cytarabine (AraC) on cognition in juvenile mice. 21 day old mice were given intrathecal injections of either saline or MTX+AraC. Hippocampal dependent memory tasks were conducted five weeks after injections. MTX+AraC treated mice showed significantly impaired cognitive function in the Morris water maze (MWM) task. MTX+AraC greatly affected hippocampal physiology. We observed significantly decreased dendritic complexity and modulations in spine morphology.;We aimed to assess effects of cranial radiotherapy on cognition in a juvenile murine model. Twenty-one- day old male C57BL/6 mice were given a single 10 Gy dose or 2 x10 Gy fractionated radiation. Five weeks following irradiation, animals were tested for hippocampus-dependent cognitive performance in MWM. A significant impairment in spatial memory retention was observed in probe trial after the first day of hidden platform training in animals that received 10 Gy or 2 x 10 Gy fractionated radiation. However, by day 5 animals that received 10 Gy showed spatial memory retention in probe trials whereas 20 Gy mice remained impaired. In addition, radiation significantly compromised dendritic complexity in dentate gyrus and CA1 hippocampal regions.;We sought to determine efficacy of Sulforaphane (SFN) to treat cognitive decline. Twenty-one- day old male C57BL/6 mice were irradiated with Small Animal Radiation Research Platform (SARRP). Animals were given 10 Gy radiation and 5 SFN injections immediately following irradiation. 24 weeks following irradiation, animals were tested for hippocampus-dependent cognitive performance. In the Morris water maze (MWM), 0 Gy and 10 Gy+SFN animals spent more time in the target quadrant than 10 Gy only treated mice. Also, 10 Gy treated mice took significantly longer to find the platform in MWM.