Azargoonjahromi Ali
Shiraz University of Medical Sciences, Shiraz, Iran.
Mol Brain. 2024 Dec 18;17(1):93. doi: 10.1186/s13041-024-01169-4.
Research on serotonin reveals a lack of consensus regarding its role in brain volume, especially concerning biomarkers linked to neurogenesis and neuroplasticity, such as ciliary neurotrophic factor (CNTF), fibroblast growth factor 4 (FGF-4), bone morphogenetic protein 6 (BMP-6), and matrix metalloproteinase-1 (MMP-1) in Alzheimer's disease (AD). This study aimed to investigate the influence of serotonin on brain structure and hippocampal volumes in relation to cognitive functions in AD, as well as its link with biomarkers like CNTF, FGF-4, BMP-6, and MMP-1. Data from 133 ADNI participants with AD included cognitive assessments (CDR-SB), serotonin measurements (Biocrates AbsoluteIDQ p180 kit, UPLC-MS/MS), and neurotrophic factors quantified via multiplex proteomics. Gray matter volume changes were analyzed using Voxel-Based Morphometry (VBM) with MRI. Statistical analyses employed Pearson correlation, bootstrap methods, and FDR-adjusted p-values (< 0.05 or < 0.01) via the Benjamini-Hochberg procedure, alongside nonparametric methods. The analysis found a positive correlation between serotonin levels and total brain (r = 0.229, p = 0.023) and hippocampal volumes (right: r = 0.186, p = 0.032; left: r = 0.210, p = 0.023), even after FDR adjustment. Higher serotonin levels were linked to better cognitive function (negative correlation with CDR-SB, r = -0.230, p = 0.024). Notably, serotonin levels were positively correlated with BMP-6 (r = 0.173, p = 0.047), CNTF (r = 0.216, p = 0.013), FGF-4 (r = 0.176, p = 0.043), and MMP-1 (r = 0.202, p = 0.019), suggesting a link between serotonin and neurogenesis and neuroplasticity. However, after adjusting for multiple comparisons and controlling for confounding factors such as age, gender, education, and APOE genotypes (APOE3 and APOE4), none of the correlations of biomarkers remained statistically significant. In conclusion, increased serotonin levels are associated with improved cognitive function and increased brain volume. However, associations with CNTF, FGF-4, BMP-6, and MMP-1 were not statistically significant after adjustments, highlighting the complexity of serotonin's role in AD and the need for further research.
关于血清素的研究表明，对于其在脑容量中的作用缺乏共识，尤其是在与神经发生和神经可塑性相关的生物标志物方面，如阿尔茨海默病（AD）中的睫状神经营养因子（CNTF）、成纤维细胞生长因子4（FGF - 4）、骨形态发生蛋白6（BMP - 6）和基质金属蛋白酶 - 1（MMP - 1）。本研究旨在调查血清素对AD患者脑结构和海马体积的影响及其与认知功能的关系，以及其与CNTF、FGF - 4、BMP - 6和MMP - 1等生物标志物的联系。来自133名ADNI研究中患有AD的参与者的数据包括认知评估（CDR - SB）、血清素测量（Biocrates AbsoluteIDQ p180试剂盒，超高效液相色谱 - 串联质谱法）以及通过多重蛋白质组学定量的神经营养因子。使用基于体素的形态测量法（VBM）结合MRI分析灰质体积变化。统计分析采用Pearson相关性分析、自助法以及通过Benjamini - Hochberg程序进行FDR校正的p值（<0.05或<0.01），同时采用非参数方法。分析发现，即使经过FDR校正，血清素水平与全脑体积（r = 0.229，p = 0.023）和海马体积（右侧：r = 0.186，p = 0.032；左侧：r = 0.210，p = 0.023）之间仍呈正相关。较高的血清素水平与更好的认知功能相关（与CDR - SB呈负相关，r = -0.230，p = 0.024）。值得注意的是，血清素水平与BMP - 6（r = 0.173，p = 0.047）、CNTF（r = 0.216，p = 0.013）、FGF - 4（r = 0.176，p = 0.043）和MMP - 1（r = 0.202，p = 0.019）呈正相关，表明血清素与神经发生和神经可塑性之间存在联系。然而，在调整多重比较并控制年龄、性别、教育程度和APOE基因型（APOE3和APOE4）等混杂因素后，生物标志物之间的相关性均无统计学意义。总之，血清素水平升高与认知功能改善和脑体积增加相关。然而，调整后与CNTF、FGF - 4
