Modifying age-related changes in mouse neuroinflammation & functional behaviors

改变小鼠神经炎症的年龄相关变化

• 批准号: 8457079
• 负责人: STEPHEN J BONASERA
• 金额: $ 52.45万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8457079
• 关键词: Address; Aerobic Exercise; Affect; Age; Aged, 80 and over; Aging; Aging-Related Process; Behavior; Behavior Therapy; Behavioral; Biological Response Modifiers; Brain; Budgets; Cell Culture Techniques; Cell physiology; Cells; Circadian Rhythms; Country; Cross-Sectional Studies; Data; Eating; Eating Behavior; Elderly; Exercise; Facies; Feeding behaviors; Fluorescence-Activated Cell Sorting; Frequencies; Gene Expression; Genes; Genetic; Graph; Gray unit of radiation dose; Health; Human; Hypothalamic structure; Immune; Immune response; Immunity; Impairment; In Situ Hybridization; Individual; Inflammation; Inflammation Mediators; Inflammatory; Intervention; Life; Longitudinal Studies; Measures; Medical; Metabolic; Metabolic Pathway; Methods; Microglia; Monitor; Movement; Mus; Nature; Nerve Degeneration; Ontology; Outcome; Persons; Physical activity; Population; Process; Property; Proteins; Quality of life; Stream; System; T-Lymphocyte; Testing; Time; Tissue-Specific Gene Expression; Tissues; Toll-like receptors; United States; Water consumption; Work; activating transcription factor 3; age related; aged; cohort; drinking; environmental enrichment for laboratory animals; experience; feeding; frontal lobe; functional status; immunocytochemistry; improved; inhibitor/antagonist; insight; lifestyle intervention; middle age; mouse model; neuroinflammation; overexpression; prevent; theories; therapeutic target; trend

The coming decades will be marked by a "graying" of the United States population. The most rapidly growing demographic group in the country is that of elderly persons, and within this group, that of the "oldest old." These trends pose significant challenges to our current medical practice. For example, the underlying causes of age-related behavioral changes remain undetermined. This application will examine the relationship between aging and changes in functional behaviors (eating, drinking, activity) by testing the hypotheses that (1) Age-related changes in mouse functional behaviors correlate with changes in gene expression regulating inflammatory & immune mediators, and (2) Exercise & environmental enrichment improve CNS functional reserve by delaying or diminishing differential expression of genes regulating immune & inflammatory processes. We propose a cross-sectional study of young, middle-aged, & aged mice. Behaviors will be monitored using a state-of-the-art system that finely classifies large behavioral data streams in a reliable and automated fashion. Measures of overall behavior, including those of circadian rhythm, time budget, & properties (duration, frequency, etc.) of movement, feeding, and drinking bouts will be analyzed. Preliminary data finds alterations in these measures similar to those seen in aging human populations. Additionally, gene expression in the hypothalamus and frontal cortex will be assessed using microarray and QT-PCR methods. Differentially expressed gene products will be classified by gene purpose. This will allow us to test whether observed behaviors correlate with changes in genes regulating immune responses rather than genes regulating activity, movement, & ingestive behaviors. We will also use graph-theory approaches to identify specific metabolic pathways (e.g., Atf3-Mapk8-Tlr2) altered in the aging hypothalamus. We also propose a longitudinal study to test whether lifestyle modifications including exercise & environmental enrichment increase CNS functional reserve. We will use similar measures of mouse behavior & gene expression as outcomes in this study. Ultimately, we anticipate that these data will provide important insight regarding the nature of aging processes in the brain, & may suggest important genetic targets for therapeutic manipulation.

未来几十年将以美国人口“老龄化”为标志。最快的 该国不断增长的人口群体是老年人，在这个群体中，“最年长的人” 这些趋势对我们当前的医疗实践提出了重大挑战。例如，潜在的 与年龄相关的行为变化的原因仍未确定。该应用程序将检查 通过测试衰老与功能行为（饮食、活动）变化之间的关系 假设 (1) 小鼠功能行为的年龄相关变化与 调节炎症和免疫介质的基因表达，以及（2）运动和环境 富集通过延迟或减少差异表达来改善中枢神经系统功能储备 调节免疫和炎症过程的基因。我们提出一项针对年轻人的横断面研究， 中年和老年小鼠。将使用最先进的系统对行为进行监控，该系统可以对行为进行精细分类 以可靠且自动化的方式提供大量行为数据流。整体行为的衡量标准，包括 昼夜节律、时间预算以及运动、进食和活动的属性（持续时间、频率等） 将分析饮酒发作。初步数据发现这些措施的变化与 人口老龄化。此外，下丘脑和额叶皮层的基因表达将 使用微阵列和 QT-PCR 方法进行评估。差异表达基因产物将被分类 通过基因目的。这将使我们能够测试观察到的行为是否与基因变化相关 调节免疫反应而不是调节活动、运动和摄入行为的基因。我们 还将使用图论方法来识别改变的特定代谢途径（例如，Atf3-Mapk8-Tlr2） 在老化的下丘脑中。我们还提出了一项纵向研究来测试生活方式的改变是否 包括锻炼和丰富环境增加中枢神经系统功能储备。我们将使用类似的 测量小鼠行为和基因表达作为本研究的结果。最终，我们预计 这些数据将提供有关大脑衰老过程本质的重要见解，并可能表明 治疗操作的重要遗传靶点。

项目成果

Increased whole cerebellar serotonin in aged C57BL/6 mice.

老年 C57BL/6 小鼠的整个小脑血清素增加。

• DOI: 10.19185/matters.201702000011
• 发表时间: 2017
• 期刊: Matters
• 作者: DeKorver,NicholasW;Lichty,Dustin;vanderHart,Marieke;Rassoulpour,Arash;Bonasera,StephenJ
• 通讯作者: Bonasera,StephenJ

Mice lacking galectin-3 (Lgals3) function have decreased home cage movement.

• DOI: 10.1186/s12868-018-0428-x
• 发表时间: 2018-05-02
• 期刊: BMC neuroscience
• 影响因子: 2.4
• 作者: Chaudoin TR;Bonasera SJ
• 通讯作者: Bonasera SJ

Decreased home cage movement and oromotor impairments in adult Fmr1-KO mice.

• DOI: 10.1111/gbb.12374
• 发表时间: 2017-06
• 期刊: Genes, brain, and behavior
• 作者: Bonasera SJ;Chaudoin TR;Goulding EH;Mittek M;Dunaevsky A
• 通讯作者: Dunaevsky A

Mobile Phone-Based Measures of Activity, Step Count, and Gait Speed: Results From a Study of Older Ambulatory Adults in a Naturalistic Setting.

• DOI: 10.2196/mhealth.5090
• 发表时间: 2017-10-03
• 期刊: JMIR mHealth and uHealth
• 影响因子: 5
• 作者: Rye Hanton C;Kwon YJ;Aung T;Whittington J;High RR;Goulding EH;Schenk AK;Bonasera SJ
• 通讯作者: Bonasera SJ

Validation of Flow Cytometry and Magnetic Bead-Based Methods to Enrich CNS Single Cell Suspensions for Quiescent Microglia.

• DOI: 10.1007/s11481-015-9628-7
• 发表时间: 2015-12
• 期刊: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
• 作者: Volden TA;Reyelts CD;Hoke TA;Arikkath J;Bonasera SJ
• 通讯作者: Bonasera SJ