McVea Andrew, Choi Jihoon, DiFilippo Alexandra, McLachlan Max, Bettcher Brecca, Zammit Matthew, Stone Charles K, Tudorascu Dana, Mukherjee Jogeshwar, Christian Bradley T
Department of Medical Physics, University of Wisconsin - Madison School of Public Health, Madison, WI, United States.
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin - Madison School of Public Health, Madison, WI, United States.
Imaging Neurosci (Camb). 2024;2. doi: 10.1162/imag_a_00397. Epub 2024 Dec 3.
Neuronal α4β2* nicotinic acetylcholine receptors (nAChRs) are stimulated by nicotine and are associated with tobacco dependence. [F]Nifene is a PET radiotracer with high specificity for α4β2* nAChRs that can be used to investigate nAChR distribution in the human brain . In this study, we investigate the dependence of sex and age on the binding of [F]nifene in nonsmoking healthy human participants. Cognitively normal participants (n = 31) were recruited into older versus younger and male versus female cohorts to investigate sex and age differences in [F]nifene binding. Distribution volume ratios (DVRs) were calculated for brain regions with known nAChR expression and compared using a multiparameter linear regression model. There was a significant association between age and decreasing thalamic DVR (p = 0.01), with the most notable difference coming from the anterior nucleus of the thalamus (p < 0.001). Outside of the thalamus, a higher [F]nifene DVR was observed with increasing age in the cerebellar grey matter (p = 0.01). No significant sex differences were observed using our linear model after multi-comparison correction. These results support including age in the experimental design and analysis of the α4β2* nAChR system in research and clinical applications.
神经元α4β2烟碱型乙酰胆碱受体（nAChRs）受尼古丁刺激，与烟草依赖有关。[F]尼非尼是一种对α4β2 nAChRs具有高特异性的正电子发射断层显像（PET）放射性示踪剂，可用于研究nAChRs在人脑中的分布。在本研究中，我们调查了性别和年龄对[F]尼非尼在不吸烟健康人类受试者中结合情况的影响。认知功能正常的受试者（n = 31）被纳入老年与年轻以及男性与女性队列，以研究[F]尼非尼结合情况的性别和年龄差异。计算已知nAChR表达的脑区的分布容积比（DVRs），并使用多参数线性回归模型进行比较。年龄与丘脑DVR降低之间存在显著关联（p = 0.01），最显著的差异来自丘脑前核（p < 0.001）。在丘脑之外，随着年龄增长，小脑灰质中观察到较高的[F]尼非尼DVR（p = 0.01）。经过多重比较校正后，使用我们的线性模型未观察到显著的性别差异。这些结果支持在研究和临床应用中，将年龄纳入α4β2* nAChR系统的实验设计和分析中。
