Giacobbo Bruno Lima, Özalay Özgün, Mediavilla Tomas, Ericsson Madelene, Axelsson Jan, Rieckmann Anna, Sultan Fahad, Marcellino Daniel
Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
Umeå Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
Front Aging Neurosci. 2022 Jan 24;14:795132. doi: 10.3389/fnagi.2022.795132. eCollection 2022.
To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a fraction of the time when compared to humans. This study aims to explore changes in dopamine D and D receptor availability and of gray matter density in striatum during aging in mice and to evaluate whether longitudinal imaging in mice may serve as a model for normal brain aging to complement cross-sectional research in humans. Mice underwent repeated structural magnetic resonance imaging (sMRI), and [C]Raclopride and [C]SCH23390 positron emission tomography (PET) was performed on a subset of aging mice. PET and sMRI data were analyzed by binding potential (BP ), voxel- and tensor-based morphometry (VBM and TBM, respectively). Longitudinal PET revealed a significant reduction in striatal BP for D receptors over time, whereas no significant change was found for D receptors. sMRI indicated a significant increase in modulated gray matter density (mGMD) over time in striatum, with limited clusters showing decreased mGMD. Mouse [C]Raclopride data is compatible with previous reports in human cross-sectional studies, suggesting that a natural loss of dopaminergic D receptors in striatum can be assessed in mice, reflecting estimates from humans. No changes in D were found, which may be attributed to altered [C]SCH23390 kinetics in anesthetized mice, suggesting that this tracer is not yet able to replicate human findings. sMRI revealed a significant increase in mGMD. Although contrary to expectations, this increase in modulated GM density may be attributed to an age-related increase in non-neuronal cells.
研究衰老的人类大脑需要大量资源和时间。因此，衰老的小鼠模型能够在相比人类少得多的时间内，为洞察大脑生物学功能的变化提供帮助。本研究旨在探索小鼠衰老过程中纹状体中多巴胺D受体和D受体可用性以及灰质密度的变化，并评估小鼠的纵向成像是否可作为正常脑衰老的模型，以补充人类的横断面研究。小鼠接受了重复的结构磁共振成像（sMRI），并对一部分衰老小鼠进行了[C]雷氯必利和[C]SCH23390正电子发射断层扫描（PET）。PET和sMRI数据通过结合潜能（BP）、基于体素和张量的形态测量法（分别为VBM和TBM）进行分析。纵向PET显示，随着时间推移，D受体的纹状体BP显著降低，而D受体未发现显著变化。sMRI表明，纹状体中调制灰质密度（mGMD）随时间显著增加，只有有限的簇显示mGMD降低。小鼠的[C]雷氯必利数据与人类横断面研究中的先前报告一致，表明可以在小鼠中评估纹状体中多巴胺能D受体的自然丧失，这与人类的估计结果相符。未发现D有变化，这可能归因于麻醉小鼠中[C]SCH23390动力学的改变，表明该示踪剂尚无法复制人类的研究结果。sMRI显示mGMD显著增加。尽管与预期相反，但这种调制GM密度的增加可能归因于非神经元细胞随年龄增长而增加。
