Neurogenesis and chronic cannabinoid exposure

神经发生和慢性大麻素暴露

• 批准号: 8445629
• 负责人: COLLEEN Cosgrove HEGG
• 金额: $ 7.68万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445629
• 关键词: Adolescence; Adolescent; Adult; Adverse effects; Affect; Aging; Aging-Related Process; Agonist; Apoptotic; Arthritis; Brain; Brain region; CNR1 gene; CNR2 gene; Cannabinoids; Cannabis; Cell Proliferation; Cessation of life; Chronic; Chronic Disease; Commit; Data; Development; Elderly; Embryo; Endocannabinoids; Exposure to; Intervention; Lead; Life; Ligands; Long-Term Effects; Marijuana; Marijuana Abuse; Measures; Mediating; Mus; Nervous system structure; Neuraxis; Neuroglia; Neurons; Olfactory Epithelium; Outcome; Pain; Pharmaceutical Preparations; Pharmacy (field); Plants; Process; Production; Public Health; Receptor Activation; Research; Research Project Grants; Staging; Stem cells; System; Testing; Tetrahydrocannabinol; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Therapeutic Uses; Time Study; addiction; adult neurogenesis; age group; aged; aging brain; analog; base; cannabinoid receptor; chronic pain; dentate gyrus; improved; indexing; mature animal; neurogenesis; prophylactic; public health relevance; receptor; Adolescence; Adolescent; Adult; Adverse effects; Affect; Aging; Aging-Related Process; Agonist; Apoptotic; Arthritis; Brain; Brain region; CNR1 gene; CNR2 gene; Cannabinoids; Cannabis; Cell Proliferation; Cessation of life; Chronic; Chronic Disease; Commit; Data; Development; Elderly; Embryo; Endocannabinoids; Exposure to; Intervention; Lead; Life; Ligands; Long-Term Effects; Marijuana; Marijuana Abuse; Measures; Mediating; Mus; Nervous system structure; Neuraxis; Neuroglia; Neurons; Olfactory Epithelium; Outcome; Pain; Pharmaceutical Preparations; Pharmacy (field); Plants; Process; Production; Public Health; Receptor Activation; Research; Research Project Grants; Staging; Stem cells; System; Testing; Tetrahydrocannabinol; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Therapeutic Uses; Time Study; addiction; adult neurogenesis; age group; aged; aging brain; analog; base; cannabinoid receptor; chronic pain; dentate gyrus; improved; indexing; mature animal; neurogenesis; prophylactic; public health relevance; receptor

DESCRIPTION (provided by applicant): Cannabinoids are increasingly being used in the treatment of chronic diseases, making it extremely important to understand their long-term effects. Cannabinoids modulate neurogenesis during development and in the adult nervous system, yet virtually nothing is known about their effects on neurogenesis in the adolescent and the aging brain. There might be differential effects of cannabinoids on neurogenesis throughout life as the central nervous system is still developing in adolescence and the capacity for neurogenesis decreases during the aging process. The objective for this project is to determine how chronic exposure to cannabinoids effects neurogenesis, measured by cell proliferation, differentiation and survival, throughout life. Our central hypothesis is that chronic exogenous modulation of the cannabinoid system will differentially alter neurogenesis depending on the developmental stage. The rationale for this research is the need to understand the long-term effects of exogenous cannabinoids on adult neurogenesis, which are currently unknown. Without this information, appropriate therapeutics for treatment of chronic diseases, such as arthritic pain, and addiction intervention can not be safely implemented. We will test our central hypothesis utilizing adolescent, adult and aged mice to ascertain the chronic effects of ¿9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana, and synthetic cannabinoids on neurogenesis in two neurogenic regions, the dentate gyrus and the olfactory epithelium. Currently, there are no medications available to treat cannabinoid addiction; however, CB1 antagonists are currently being developed as potential therapeutic agents. Therefore, we will also assess the chronic effects of CB1 antagonists on neurogenesis. In addition, cannabinoids modulate whether progenitor cells commit to neurons or glia in both post-natal and adult animals. Chronic exposure to exogenous cannabinoids could significantly alter the proportion of progenitor cells that mature into glia as compared to neurons, regardless of the developmental stage. Change in the cellular composition of a brain region could adversely affect function. This proposed small research project will provide a detailed understanding of the chronic effects of cannabinoids on neurogenesis throughout development. Information gained may delineate both positive, neuroprotective effects, as in increased neurogenesis in the aged, as well as detrimental effects, as in altered neurogenesis in the adolescent. The overall contribution will be significant in that it will provide the basis for the development of improved and safe therapeutic strategies.

描述（由适用提供）：大麻素越来越多地用于治疗慢性疾病，因此了解其长期影响非常重要。大麻素在发育过程和成人神经系统中调节神经发生，但实际上对它们对青少年和衰老大脑的神经发生的影响几乎一无所知。大麻素对整个生命的神经发生可能存在差异作用，因为中枢神经系统仍在青少年中发展，并且在衰老过程中神经发生的能力降低。该项目的目的是确定长期暴露于大麻素的暴露如何通过细胞增殖，分化和存活量影响神经发生。我们的中心假设是，大麻素系统的慢性外源调节将根据发育阶段改变神经发生。这项研究的基本原理是需要了解外源性大麻素对成人神经发生的长期影响，目前尚不清楚。没有这些信息，无法安全地实施用于治疗慢性疾病的适当治疗，例如关节炎和成瘾干预。我们将利用青少年，成年和老年小鼠测试中央假设，以确定€9-四氢大麻醇（THC）的慢性影响，大麻的主要心理活性成分以及合成大麻素对两个神经源性区域的神经生成的慢性影响，在两个神经源性区域中，齿状甲状酸酯和齿状gyrus和Olfartory Epithium。目前，没有可用于治疗大麻素成瘾的药物。但是，目前正在开发CB1拮抗剂作为潜在的治疗剂。因此，我们还将评估CB1拮抗剂对神经发生的慢性影响。此外，大麻素可以调节祖细胞是否在产后和成年动物中都致力于神经元或神经胶质。与神经元相比，长期暴露于表达性大麻素可能会显着改变成熟到神经胶质的祖细胞的比例。大脑区域细胞组成的变化可能会对功能产生不利影响。该提出的小型研究项目将详细了解大麻素对整个发育中神经发生的慢性影响。获得的信息可能会描绘出阳性，神经保护作用，就像在青春期神经发生的改变和有害作用中增加的神经发生和有害作用一样。总体贡献将是重要的，因为它将为发展改进和安全的治疗策略提供基础。