Hippocampal Extracellular Matrix Regulates Glia-Neuron Crosstalk after Injury

海马细胞外基质在损伤后调节胶质细胞-神经元串扰

基本信息

批准号：
10457472
负责人：
Maral Tajerian
金额：
$ 15.4万
依托单位：
QUEENS COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10457472
关键词：
Address Adult Affect Anatomy Animal Behavior Area Atomic Force Microscopy Behavioral Sciences Biochemical Biochemistry Biomedical Research Biophysics Brain CCL7 gene Cell Culture System Cell Culture Techniques Cell physiology Cells Clinical Cognition Data Dendrites Development Environment Event Extracellular Matrix Funding Goals Grant Hippocampus (Brain)Immunohistochemistry Impaired cognition In Vitro Injury Knowledge Laboratories Limbic System Measures Memory Memory impairment Mental disorders Mentors Mentorship Methods Microdialysis Microscopy Mission Modeling Morphology Mus Nature Neuraxis Neuroglia Neuromodulator Neuronal Plasticity Neurons Nociception Pain Pain Clinics Pain management Pathway interactions Patients Peripheral Pharmacology Physiology Population Prevention Proteins Research Resistance Role Scanning Electron Microscopy Schools Sensory Severities Signal Transduction Structure Students Technical Expertise Techniques Tibial Fractures TimeLine Training Training Programs Trauma Underrepresented Minority United States National Institutes of Health Universities Western Blotting affective disturbance anxiety-like behavior base career cell type central pain chronic pain college comorbidity ethnic diversity experience experimental study extracellular graduate student in vivo innovation limb fracture member minority student multidisciplinary multimodality neuroinflammation neuronal growth new therapeutic target novel strategies pain chronification pre-clinical programs socioeconomic diversity therapeutic target undergraduate student

项目摘要

PROJECT SUMMARY Significance: Chronic pain affects 30% of the adult population in the USA and presents with multiple co-morbid psychiatric disorders, including mood alterations and cognitive impairment. Despite the severity of this problem, clinicians often rely on a “trial and error” approach to find a strategy that provides some measure of relief. This is mainly because most pain treatments were implemented based on clinical observations rather than a mechanistic understanding of chronic pain. One of the pivotal mechanisms that could explain the chronification of pain as well as its resistance to classical treatment is the concept of pain centralization, where initial sensory events following trauma can gradually alter the central nervous system (CNS), resulting in amplified pain and/or aberrant pain that exists without peripheral sensitization. However, most of the research in this area focuses on cellular mechanisms and overlooks the extracellular matrix (ECM) in which these cells function. The proposed research aims to delineate the role of brain ECM components in pain-related cellular and structural plasticity, thereby expanding our knowledge of the effects of chronic pain on the brain. Innovation: The proposed study is multimodal in nature and incorporates techniques related to animal behavior, cell physiology, biochemistry, cell culture, pharmacology, and microscopy. For instance, ECM rigidity will be assessed by using structural (microarchitectural analysis following scanning electron microscopy and physical rigidity using atomic force microscopy) as well as biochemical analyses (immunohistochemistry and protein quantification). Similarly, the role of specific ECM components will be evaluated both in vivo (pharmacology) and in vitro (using a unique decellularized brain substrate for neuronal culture). Upon the completion of the proposed studies, the developed toolset can be a useful asset in studying brain areas outside the hippocampus. Participation of underrepresented minorities in the biomedical/behavioral sciences: Consistent with the NIH’s mission of training and graduating students from groups nationally underrepresented in biomedical research, the current proposal specifically targets the diverse student body of Queens College, CUNY. Queens College boasts high levels of ethnic and socioeconomic diversity and Dr. Tajerian is committed to mentoring the many undergraduate and graduate students in her department. She has extensive mentorship experience both at McGill at Stanford universities, and her current laboratory members include students from diverse backgrounds. Dr. Tajerian is also part of the MARC-U*STAR mentoring program. Maximizing Access to Research Careers is an Undergraduate Student Training program in Academic Research. It is the first NIH program specifically focused on directing under-represented minority students toward graduate school and biomedical research careers. Timeline and developmental objectives: The proposed timeline for the outlined experiments is 3 years. Data collected for the duration of this grant, in addition to the acquired technical expertise, will be instrumental in the acquisition of R01 level funding in the field of brain extracellular matrix alterations in chronic pain.

项目摘要意义：慢性疼痛影响美国的30％的成年人口，并伴有多个合并症精神疾病，包括情绪改变和认知障碍。尽管有这个问题的严重性，临床医生通常依靠一种“反复试验”方法来找到一种策略，以提供一些救济度量。这主要是因为大多数疼痛治疗是基于临床观察而不是机械的了解慢性疼痛。可以解释疼痛的调查的关键机制之一疼痛集中的概念及其对经典治疗的抵抗力，初始感觉事件造成创伤后会逐渐改变中枢神经系统（CNS），从而导致疼痛和/或异常没有周围敏感性的疼痛。但是，该领域的大多数研究都集中在细胞上机理并忽略了这些细胞起作用的细胞外基质（ECM）。拟议的研究旨在描述脑ECM成分在疼痛相关的细胞和结构可塑性中的作用，从而扩大我们对慢性疼痛对大脑的影响的了解。创新：拟议的研究本质上是多模式的，并结合了与动物行为有关的技术，细胞生理学，生物化学，细胞培养，药理学和显微镜。例如，ECM刚度将是通过使用结构（扫描电子显微镜和物理后的微构造分析）评估使用原子力显微镜）以及生化分析（免疫组织化学和蛋白质量化）。同样，将评估特定ECM组件的作用，同时在体内（药理学）并在体外（使用独特的脱细胞脑底物进行神经元培养）。完成后拟议的研究，开发的刀具集可能是研究海马以外的大脑区域的有用资产。代表性不足的少数民族参与生物医学/行为科学：与 NIH的使命是培训和毕业的学生，来自全国人数不足的生物医学成员研究，当前的建议专门针对CUNY皇后学院的潜水员学生团体。皇后大学拥有高水平的种族和社会经济多样性，塔杰里安博士致力于指导她的部门的许多本科生和研究生。她在斯坦福大学的麦吉尔及其现任实验室成员包括来自潜水员背景的学生。 Tajerian博士也是Marc-U*Star心理计划的一部分。最大化研究职业的机会是学术研究的本科生培训计划。这是第一个专门的NIH计划专注于将代表性不足的少数族裔学生带入研究生院和生物医学研究职业。时间表和发展目标：概述实验的建议时间表为3年。数据除了获得后的技术专长外，还将在这笔赠款期间收集，还将在慢性疼痛中脑外部基质改变领域中R01水平资金的获取。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rapamycin Augmentation of Chronic Ketamine as a Novel Treatment for Complex Regional Pain Syndrome.

雷帕霉素增强慢性氯胺酮作为复杂区域疼痛综合征的新型治疗方法。

DOI：
10.7759/cureus.43715
发表时间：
2023-08
期刊：
Cureus
影响因子：
0
作者：
Sharma A;Tajerian M;Berner J
通讯作者：
Berner J

Persistent inflammatory pain is linked with anxiety-like behaviors, increased blood corticosterone, and reduced global DNA methylation in the rat amygdala.

DOI：
10.1177/17448069221121307
发表时间：
2022-04
期刊：
MOLECULAR PAIN
影响因子：
3.3
作者：
Spinieli, Richard L.;Cazuza, Rafael Alves;Sales, Amanda Juliana;Gomes Carolino, Ruither Oliveira;Martinez, Diana;Anselmo-Franci, Janete;Tajerian, Maral;Leite-Panissi, Christie R. A.
通讯作者：
Leite-Panissi, Christie R. A.

Garments and Footwear for Chronic Pain.