Inflammation-Induced Brain Changes in Breast Cancer Patients Studied with MRS

MRS 研究乳腺癌患者炎症引起的大脑变化

• 批准号: 9263681
• 负责人: Candace C. Fleischer
• 金额: $ 2.05万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263681
• 关键词: Adverse effects; Affect; Aftercare; Anterior; Antidepressive Agents; Basal Ganglia; Behavior Control; Behavior assessment; Behavioral; Behavioral Mechanisms; Behavioral Symptoms; Bilateral; Blood; Brain; Brain region; Breast Cancer Patient; Breast Cancer Treatment; Chemical Shift Imaging; Chronic; Clinical; Cognition; Complement; Data; Diagnosis; Dorsal; Exhibits; Fatigue; Glutamate Metabolism Pathway; Glutamates; Glutamine; Glutathione; Goals; Immune system; In Vitro; Inflammation; Inflammatory; Interferon-alpha; Link; Magnetic Resonance Spectroscopy; Major Depressive Disorder; Malignant Neoplasms; Measurement; Measures; Mediating; Mediator of activation protein; Mental Depression; Moods; Motivation; Necrosis; Neuraxis; Neurobehavioral Manifestations; Neurotransmitters; Patients; Peripheral; Pharmaceutical Preparations; Plasma; Proteins; Recruitment Activity; Reproducibility; Research; Research Personnel; Research Training; Resolution; Role; Spectrum Analysis; Symptoms; Techniques; Testing; Universities; Validation; Withholding Treatment; Woman; Work; anticancer research; base; chemotherapy; cingulate cortex; cognitive function; common symptom; cytokine; design; experience; improved; in vivo; inflammatory marker; insight; interest; investigator training; malignant breast neoplasm; mood regulation; neurobehavioral; neuropsychiatric disorder; neurotransmission; novel; public health relevance; receptor; secondary analysis; tumor; white matter

 DESCRIPTION (provided by applicant): Breast cancer is one of the most common cancers affecting women in the U.S. Behavioral symptoms such as depression and fatigue are common symptoms among breast cancer patients receiving chemotherapy treatment and can persist long after treatment cessation. The underlying mechanism for the behavioral symptoms is unknown, however previous work has demonstrated a relationship between peripheral inflammation and persisting behavioral and cognitive symptoms. For example, inflammatory cytokines released as a result of immune system activation by chemotherapy treatment can target and interact with multiple brain regions known to control behavior, mood, and cognition. While several mechanisms for inflammation-induced behavioral changes have been proposed, strong evidence supports the role of glutamate, the primary excitatory neurotransmitter, as the link between peripheral inflammation and behavioral changes. Recent work has shown that immune system activation following administration of the proinflammatory cytokine, interferon-alpha, resulted in increased central nervous system (CNS) glutamate concentrations measured with magnetic resonance spectroscopy (MRS), further supporting the role of glutamate dysregulation as a mediator between inflammation and behavioral changes. The working hypothesis of this proposal is that breast cancer patients exposed to chemotherapy will show higher glutamate concentrations in the CNS that will be associated positively with inflammatory markers and behavioral symptoms including depression and fatigue. To test this hypothesis, multi-voxel MRS will be used to measure glutamate concentrations in the bilateral basal ganglia, dorsal anterior cingulate cortex, and subcortical white matter in patients with breast cancer who have undergone chemotherapy treatment, breast cancer patients who have not undergone chemotherapy, and healthy controls without breast cancer. To enable spectral resolution of glutamine and glutathione, neuroprotective metabolites synthesized from glutamate, a new 2D MRS technique will be implemented. Secondary analysis will be performed on behavioral assessment data and plasma inflammatory markers from blood draws. The results of this research will provide important insight into the association between inflammation, glutamate and related metabolites, and behavioral symptoms in breast cancer patients undergoing chemotherapy treatment. Additionally, the proposed research plan will provide training for the investigator in MRS techniques and applications, introduce the first in vivo 2D MRS technique to be used at Emory University, and aid the investigator in developing an independent line of inquiry into applications of MRS for neurobehavioral studies of cancer and its treatment.