Nicotinic modulation of brain physiology and cognition in human aging

烟碱对人类衰老过程中大脑生理和认知的调节

• 批准号: 416397042
• 负责人: Dr. Min-Fang Kuo, Ph.D.
• 金额: --
• 依托单位: Projektgruppe Neuromodulation
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416397042?language=en
• 关键词: Nicotinic; modulation; brain; physiology; cognition

The cholinergic system regulates neuroplasticity and a broad range of cognitive-behavioural functions including perception, attention, learning, and memory, most probably via enhancing the signal-to-noise ration in neuronal networks. Disruption to cholinergic neurotransmission results in cognitive performance deterioration, which is observed in nicotine addiction, dementia related to neurodegeneration, but also in normal aging. Especially nicotinic receptor subtypes play a relevant role in cognition-relevant brain physiology. Accordingly, nicotinic agents have been shown to restore plasticity and cognitive impairment in case of nicotininc receptor hypo-activation, such as in smokers under nicotine withdrawal. Nicotine also revealed cognitive benefits in old subjects. Detailed knowledge however about the contribution of nicotinic receptors to these functions, and respective physiological mechanisms is scarce. We will investigate the specific impact of nicotinic receptor activation on neuroplasticity and cognitive functions in young/old age and smokers/non-smokers, and to explore the neurophysiological mechanism underlying hypothesized state-dependent differences of effects, including a presumed protective/restituting impact. Neuroplasticity will be induced in young and old healthy humans including both, smoking and non-smoking subjects. Since the impact of nicotine on plasticity and cognitive functions seems to be largely driven by nicotinic receptors with calcium channel properties, varenicline, a nicotinic α4β2 and α7 agonist will be applied to study nicotinergic modulation of neuroplasticity. We will further elucidate the association between physiological plasticity and behavioral performance, with particular focus on network connectivity which is suggested to reflect the dynamics of learning and memory processes at the neurophysiological level. Motor learning task will be implemented with monitoring and modifying task-related brain oscillations and connectivities. The nicotinergic effect on cortical plasticity, network connectivity, and cognition will be correlated to obtain systemic knowledge about the neueophysiological basis of nicotinic modulation on cognition. A better understanding of the mechanisms underlying age-related nicotinic modulation on both cognition and neurophysiology of human brain will help to develop more effective strategy for the prevention or restitution of functional decline caused by senescence.

胆碱能系统调节神经可塑性和广泛的认知行为功能，包括感知、注意、学习和记忆，最有可能通过增强神经网络中的信噪比。破坏胆碱能神经传递导致认知能力下降，这在尼古丁成瘾、与神经变性相关的痴呆中都可以观察到，但在正常衰老中也可以观察到。特别是烟碱受体亚型在认知相关的脑生理学中起着相关的作用。因此，尼古丁制剂已被证明在尼古丁受体低激活的情况下，如尼古丁戒断的吸烟者，可以恢复可塑性和认知障碍。尼古丁对老年人的认知也有好处。然而，关于尼古丁受体对这些功能的贡献以及各自的生理机制的详细知识很少。我们将研究尼古丁受体激活对年轻人/老年人和吸烟者/非吸烟者的神经可塑性和认知功能的具体影响，并探索假设的状态依赖性影响差异的神经生理机制，包括假设的保护/恢复影响。神经可塑性将在年轻人和老年人健康人群中被诱导，包括吸烟和不吸烟的受试者。由于尼古丁对可塑性和认知功能的影响似乎主要是由具有钙通道特性的尼古丁受体驱动的，因此我们将利用尼古丁α4β2和α7激动剂varenicline来研究尼古丁能调节神经可塑性。我们将进一步阐明生理可塑性与行为表现之间的关系，特别关注网络连通性，这被认为反映了神经生理水平上学习和记忆过程的动态。运动学习任务将通过监测和修改与任务相关的大脑振荡和连接来实现。烟碱对皮质可塑性、网络连通性和认知的影响将相互关联，以获得有关烟碱调节认知的神经生理基础的系统知识。更好地了解与年龄相关的尼古丁对人类大脑认知和神经生理的调节机制，将有助于制定更有效的策略来预防或恢复衰老引起的功能衰退。