(S047) Radiotherapy vs Chemotherapy Effects on Neuronal Architecture and Spine Density in the Hippocampus

OncologyOncology Vol 29 No 4_Suppl_1
Volume 29
Issue 4_Suppl_1

Exposure to chemotherapy or RT disrupts the formation and establishment of proper synaptic connections by causing significant alterations in neuronal structure that compromise neurotransmission and cognition.

Nevine Hanna, MD, MPH, Munjal Acharya, PhD, Charles Limoli, PhD; University of California, Irvine

PURPOSE: Studies have shown that cognitive function is compromised by both radiation treatment (RT) and the use of chemotherapy (ie, the “chemobrain” phenomenon). Given that advancements in diagnosis, beam delivery, and drug treatments have extended long-term cancer survivorship, it has become increasingly critical to address the extent and persistence of, and neurobiological mechanisms underlying, cognitive dysfunction associated with cancer treatments. Through immunofluorescence studies in mice, our lab previously established that irradiation elicits significant reductions in neuronal morphology. In the present study, we examine the consistency of the effects of radiation or chronic cyclophosphamide (CYP) treatment, a commonly prescribed chemotherapeutic agent, on animal behavior and neuronal morphology via different staining techniques.

METHODS: Adult athymic nude rats were treated with 9 Gy of x-rays every other day to a total of 27 Gy (biologically effective dose [BED] = 108 Gy) or with CYP (100 mg/kg) once weekly for 4 weeks and compared with sham-irradiated or saline controls, respectively. At 1 month posttreatment, animals were administered hippocampus- and cortex-dependent cognitive tasks, including novel place recognition (NPR) and a temporal order (TO) task. Following cognitive testing, immunohistochemical staining was used to trace immature (doublecortin, DCX+) and mature (Golgi-Cox–impregnated) neurons in the brain for an assessment of neuronal morphology in the CA1 region. Spine density was also counted to delineate the number of long/thin, mushroom, and stubby spines in the same region.

RESULTS: Both irradiated and CYP-treated rats showed significant decrements in learning and memory when assessed on both the NPR and TO tasks. CYP-treated animals were impaired in hippocampus-dependent place recognition memory and cortex-dependent recency memory compared with controls. Quantification of ultrastructural parameters of neurons in the hippocampus using Neurolucida software indicated compromised dendritic morphology in the immature (DCX+) and mature (Golgi-Cox) neurons in the CA1 hippocampal region. Chronic CYP treatment (n = 20) led to significant reductions in the apical dendritic volume (P = .0033), basal total dendritic length (P = .0161), endings (P = .0352), volume (P = .0004), and complexity (including branching and three-dimensional morphology; P = .01) compared with sham. Early analysis (n = 5) is also showing similar significance in the irradiated cohort. With regard to spine density, overall group effects were found for altered numbers of long/thin (P = .0079), mushroom (P = .0048), and stubby (P = .006) spine types in the CA1 region.

CONCLUSIONS: Exposure to chemotherapy or RT disrupts the formation and establishment of proper synaptic connections by causing significant alterations in neuronal structure that compromise neurotransmission and cognition.

Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org

Articles in this issue

(P005) Ultrasensitive PSA Identifies Patients With Organ-Confined Prostate Cancer Requiring Postop Radiotherapy
(P001) Disparities in the Local Management of Breast Cancer in the United States According to Health Insurance Status
(P002) Predictors of CNS Disease in Metastatic Melanoma: Desmoplastic Subtype Associated With Higher Risk
(P003) Identification of Somatic Mutations Using Fine Needle Aspiration: Correlation With Clinical Outcomes in Patients With Locally Advanced Pancreatic Cancer
(P004) A Retrospective Study to Assess Disparities in the Utilization of Intensity-Modulated Radiotherapy (IMRT) and Proton Therapy (PT) in the Treatment of Prostate Cancer (PCa)
(S001) Tumor Control and Toxicity Outcomes for Head and Neck Cancer Patients Re-Treated With Intensity-Modulated Radiation Therapy (IMRT)-A Fifteen-Year Experience
(S003) Weekly IGRT Volumetric Response Analysis as a Predictive Tool for Locoregional Control in Head and Neck Cancer Radiotherapy 
(S004) Combination of Radiotherapy and Cetuximab for Aggressive, High-Risk Cutaneous Squamous Cell Cancer of the Head and Neck: A Propensity Score Analysis
(S005) Radiotherapy for Carcinoma of the Hypopharynx Over Five Decades: Experience at a Single Institution
(S002) Prognostic Value of Intraradiation Treatment FDG-PET Parameters in Locally Advanced Oropharyngeal Cancer
(P006) The Role of Sequential Imaging in Cervical Cancer Management
(P008) Pretreatment FDG Uptake of Nontarget Lung Tissue Correlates With Symptomatic Pneumonitis Following Stereotactic Ablative Radiotherapy (SABR)
(P009) Monte Carlo Dosimetry Evaluation of Lung Stereotactic Body Radiosurgery
(P010) Stereotactic Body Radiotherapy for Treatment of Adrenal Gland Metastasis: Toxicity, Outcomes, and Patterns of Failure
(P011) Stereotactic Radiosurgery and BRAF Inhibitor Therapy for Melanoma Brain Metastases Is Associated With Increased Risk for Radiation Necrosis
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