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Quantifying Cognitive Decrements Caused by Cranial Radiotherapy
Published on: October 18, 2011
Cranial irradiation impairs juvenile social memory and modulates hippocampal physiology
Jamila Newton1, Taurean Brown2, Christa Corley2
1California State University, Stanislaus, Turlock, CA 95382, United States.
Insights
Cranial radiation therapy in pediatric acute lymphoblastic leukemia survivors impairs social behavior and reduces mushroom spine density in the hippocampus. This neurocognitive dysfunction is linked to metabolic and signaling pathway dysregulation.
Area of Science:
- Neuroscience
- Oncology
- Radiology
Background:
- Cranial radiotherapy is a standard prophylaxis for pediatric acute lymphoblastic leukemia (ALL).
- Childhood ALL survivors treated with cranial radiotherapy face increased risks of neurocognitive deficits.
- Radiation-induced normal tissue responses are implicated in cognitive changes post-therapy.
Purpose of the Study:
- To investigate the impact of cranial radiation on social behavior and hippocampal neuronal morphology in adult mice.
- To understand the molecular mechanisms underlying radiation-induced neurocognitive dysfunction.
Main Methods:
- Adult male mice received a single 10-Gy X-ray cranial radiation dose.
- Behavioral testing using the Three-Chamber Sociability paradigm assessed social discrimination.
- Proteomic analysis identified dysregulated metabolic and signaling pathways.
- Hippocampal neuronal morphology, specifically mushroom spine density, was examined.
Main Results:
- Irradiated mice exhibited impaired social discrimination, failing to differentiate between familiar and stranger mice.
- Proteomic analysis revealed dysregulation in pathways including mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis.
- A significant decrease in mushroom spine density was observed in the hippocampus (Cornu Ammonis 2).
Conclusions:
- Cranial radiation negatively affects social behavior and neuronal morphology in the hippocampus.
- Molecular pathway dysregulation contributes to radiation-induced neurocognitive deficits.
- Reduced mushroom spine density in the hippocampus is associated with impaired sociability processing.
Abstract:
Cranial and craniospinal irradiation are the oldest central nervous system prophylaxis treatments considered for pediatric patients with acute lymphoblastic leukemia (ALL). However, survivors of childhood ALL that received cranial radiotherapy are at increased risk for deficits in neurocognitive skills. The continuous and dynamic response of normal tissue after irradiation has been identified as one of the causative factors for cognitive changes after cranial radiation therapy. The aim of our study was to investigate the radiation effects on social behavior and neuronal morphology in the hippocampus of adult mice. Twenty-oneday-old male C57BL/6 mice were irradiated with the small-animal radiation research platform (SARRP). Animals were given a single 10-Gy dose of radiation of X-ray cranial radiation. One month following irradiation, animals underwent behavioral testing in the Three-Chamber Sociability paradigm. Radiation affected social discrimination during the third stage eliciting an inability to discriminate between the familiar and stranger mouse, while sham successfully spent more time exploring the novel stranger. Proteomic analysis revealed dysregulation of metabolic and signaling pathways associated with neurocognitive dysfunction such as mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis signaling. We observed significant decreases in mushroom spine density in the Cornu Ammonis 2 of the hippocampus, which is associated with sociability processing.
