Effects of social isolation and enrichment on communication impairment in a translational model of PD

社交隔离和丰富对 PD 转化模型中沟通障碍的影响

基本信息

批准号：
10459020
负责人：
Courtney Kuehn Broadfoot
金额：
$ 0.25万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
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：
2020-08-21 至 2022-08-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10459020
关键词：
Acoustics Affect Age Age-Months Anhedonia Animal Behavior Anxiety Area Attenuated Basal Ganglia Behavior Behavioral Assay Biological Assay Brain Brain Pathology Brain Stem Brain region Catecholamines Characteristics Child Cognition Cognitive Communication Communication impairment Communicative Dysfunctions Complex Degenerative Disorder Detection Disease Disease Progression Dopamine Emotional Environmental Risk Factor Experimental Designs Foundations Functional disorder Future Goals Health High Pressure Liquid Chromatography High Prevalence Human Impaired cognition Impairment Individual Intervention Knowledge Larynx Lead Life Limb structure Measures Medial Mental Depression Modeling Motor Neurobiology Neurologic Neurotransmitters Norepinephrine Outcome Parkinson Disease Pathology Pathway interactions Performance Personal Satisfaction Population Predictive Factor Prefrontal Cortex Quality of life Randomized Rattus Regulation Research Rodent Role Serotonin Social Conditions Social Environment Social Interaction Social isolation Socialization Speech Spouses Substantia nigra structure Sucrose System Testing Time TimeLine Training Ultrasonics Ventral Tegmental Area Well in self Work behavior test brain tissue cognitive ability cognitive function cognitive skill combat early onset experience improved neurochemistry neuropathology noradrenergic novel object recognition preference preservation psychosocial relating to nervous system scaffold social social communication translation to humans translational model treatment group vocalization

项目摘要

Abstract Parkinson disease (PD) is a complex, neurodegnerative disorder characterized by limb motor, sensorimotor, and non-motor features including anxiety, depression, and cognitive dysfunction. 90% of individuals with PD experience significant communication deficits that diminish quality of life. Vocal function, cognitive skill, and regulation of anxiety/depression are essential for meaningful social interactions; thus, individuals with PD often experience debilitating social isolation. How socially-isolating living conditions impact vocal communication, cognitive abilities, and well-being in PD, however, is not known, especially in early and mid-stage disease. Further, the underlying brain pathology that modulates these behaviors is not fully described. Because of these critical gaps in knowledge, deficits in communication, cognition, and anxiety/depression remain largely under- treated. We propose to study how social interaction relates to vocal function, cognition, well-being, and neuropathological progression using a validated rat model of early-onset PD (Pink1-/-). This model recapitulates vocal communication deficits with laryngeal and brainstem pathology that follows an onset and progressive timeline analogous to humans. Our central hypotheses are that social isolation further contributes to vocal degradation, and enhancing vocal opportunities with a social enrichment intervention will slow the onset and progression of vocal communication deficits, improve cognitive function, and decrease anxiety and anhedonia, a marker for depression. Further, we hypothesize that neurochemical content in areas critical for speech motor and cognitive/emotional control (the ventral tegmental area, medial prefrontal cortex, and substantia nigra) will be altered by social condition. We propose two specific aims: Aim 1 will quantify the impact of social condition on vocal communication, cognition, anxiety, and anhedonia in Pink1-/- and WT rats. Pink1-/- and wildtype (WT) control rats will be randomly assigned to 3 experimental treatment conditions: (1) control, (2) isolation, and (3) social enrichment (implemented 5x per week to facilitate social and vocal opportunities with conspecifics). Using established rat behavior tests, vocal communication, cognition, anxiety, and anhedonia will be quantified and statistically compared at the following disease stages: prodromal (2, 4 mo of age), early (6 mo), and mid-stage (8,10 mo). Additionally, Aim 2 will determine how social condition affects catecholamine concentrations in the ventral tegmental area, medial prefrontal cortex, and substantia nigra of Pink1-/- and WT rats. Brain tissue from these regions will be assayed for dopamine, norepinephrine, and serotonin concentrations using high pressure liquid chromatography at 10 mo. This work is timely and significant as it will lead to a better understanding of how social isolation contributes to the complex pathology of PD-related communication dysfunction and provide foundational knowledge of how social enrichment may attenuate these deficits and change brain neurochemistry. The overarching goal of my training is to provide a foundation to conduct research that has a direct translation to human health.

抽象的帕金森氏病（PD）是一种复杂的，神经降解性疾病，特征在于肢体运动，感觉运动，和非运动特征，包括焦虑，抑郁和认知功能障碍。 90％的PD患者经历降低生活质量的大量沟通不足。人声功能，认知技能和焦虑/抑郁的调节对于有意义的社会互动至关重要；因此，经常患有PD的人经历使社会隔离的衰弱。社会隔离的生活条件如何影响声音交流，然而，认知能力和PD中的福祉尚不清楚，尤其是在早期和中期疾病中。此外，调节这些行为的潜在脑病理学并未得到充分描述。因为这些知识，沟通缺陷，认知和焦虑/抑郁的关键差距在很大程度上保持不足治疗。我们建议研究社会互动与声乐功能，认知，幸福感以及使用验证的早期发作PD的大鼠模型（PINK1 - / - ）的神经病理学进展。这个模型通过喉和脑干病理学概括声沟通缺陷，遵循发作和发作渐进的时间表类似于人类。我们的核心假设是社会隔离进一步贡献通过社交富集干预措施来发声降解，并增强声乐机会会减慢声音交流缺陷的发作和进展，改善认知功能，减轻焦虑和 Anhedonia，抑郁症的标志。此外，我们假设在至关重要的区域中的神经化学内容言语运动和认知/情绪控制（腹侧段区域，内侧前额叶皮层和尼格拉族将通过社会状况改变。我们提出了两个具体目标：AIM 1将量化社会状况对PINK1 - / - 和 wt老鼠。 pink1 - / - 和野生型（wt）对照大鼠将随机分配给3个实验治疗条件：（1）控制，（2）隔离和（3）社会丰富（每周实施5倍，以促进社会和具有同种的声音机会）。使用已建立的大鼠行为测试，人声交流，认知，焦虑症和抗甲氧化症将在以下疾病阶段进行量化和统计学比较：前驱（2，4 Mo年龄），早期（6个月）和中期（8,10 mo）。此外，AIM 2将决定社交疾病会影响腹侧侧距区域的儿茶酚胺浓度，内侧前额叶皮层，和pink1 - / - 和wt大鼠的黑质。这些区域的脑组织将用于多巴胺，使用高压液相色谱分10个月的去甲肾上腺素和5-羟色胺浓度。这项工作及时和意义，因为它将更好地理解社会隔离如何对与PD相关的通信功能障碍的复杂病理学，并提供有关如何社会富集可能会削弱这些缺陷并改变脑神经化学。我的总体目标培训是为了进行直接转化为人类健康的研究提供基础。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effects of social isolation on 50-kHz ultrasonic vocalizations, affective state, cognition, and neurotransmitter concentrations in the ventral tegmental and locus coeruleus of adult rats.

DOI：
10.1016/j.bbr.2022.114157
发表时间：
2023-02-02
期刊：
BEHAVIOURAL BRAIN RESEARCH
影响因子：
2.7
作者：
Broadfoot, Courtney K.;Lenell, Charles;Kelm-Nelson, Cynthia A.;Ciucci, Michelle R.
通讯作者：
Ciucci, Michelle R.

Biological and Acoustic Sex Differences in Rat Ultrasonic Vocalization.