Dopamine D1-signaling modulates maintenance of functional network segregation in aging

IF 1.7 Q3 CLINICAL NEUROLOGY Aging brain Pub Date : 2023-01-01 DOI:10.1016/j.nbas.2023.100079
Robin Pedersen , Jarkko Johansson , Alireza Salami
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引用次数: 2

Abstract

Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age.

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多巴胺D1信号调节衰老过程中功能网络分离的维持
过去的研究表明,随着个体年龄的增长,网络内部的连接会减少,网络之间的连接会增加,这种模式被称为功能去分化。虽然减少网络分离背后的机制尚不完全清楚,但有证据表明,多巴胺(DA)系统中与年龄相关的差异可能起着关键作用。DA D1受体(D1DR)是多巴胺能系统中最丰富且对年龄敏感的受体亚型,已知其调节突触活性并增强神经元信号的特异性。在DyNAMiC项目(N=180,20-79y)的这项研究中,我们开始研究年龄、功能连接和多巴胺D1DR可用性之间的相互作用。使用多元偏最小二乘(PLS)的新应用,我们发现年龄较大和D1DR可用性较低同时与网络内连接减少和网络间连接增加的模式有关。在大规模网络中表现出更大独特性的个体表现出更有效的工作记忆。根据维持假设,我们发现尾状体中D1DR较大的老年人与D1DR较少的年龄匹配的同龄人相比,连接体的去分化较少,工作记忆更大。这些发现表明,多巴胺能神经传递在衰老过程中的功能去分化中起着重要作用,并对老年人的工作记忆功能产生影响。
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Aging brain
Aging brain Neuroscience (General), Geriatrics and Gerontology
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