Altered Glutamate Gene-enriched Functional Connectivity in Aging During Movie-watching
Poster No:
892
Submission Type:
Abstract Submission
Authors:
Yulin He1,2, Zihao Zheng1,2, Ao Xie1,2, Haiyang Sun1,2, Yulan Zhou1,2, jianfu li1,2, Cheng Luo1,2, Li Dong1,2
Institutions:
1The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, Chengdu, China, 2School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
First Author:
Yulin He
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Co-Author(s):
Zihao Zheng
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Ao Xie
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Haiyang Sun
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Yulan Zhou
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
jianfu li
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Cheng Luo
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Li Dong
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China|School of Life Science and Technology, University of Electronic Science and Technology of China
Chengdu, China|Chengdu, China
Introduction:
The aging factor plays an increasingly significant role in changes to functional connectivity. Recent study have shown that aging has a large impact on connectivity within specific functional networks in the brain (Geerligs et al., 2015). The glutamate receptor is reported to be associated with cognition and brain aging (Mecca et al., 2021). Glutamate Dehydrogenase 1 (GLUD1), which is a key regulator of glutamate metabolism is encoded by the GLUD1 gene (Asraf et al., 2023). Glutamate Dehydrogenase 2 (GLUD2) gene is a human gene involved in glutamate metabolism, which may have contributed to human brain evolution by enhancing synaptic plasticity and metabolic processes central to cognitive functions (Spanaki et al., 2024). However, the potential functional network changes in old people related to specific molecular systems of the glutamate gene are still unclear. Here we used a new method to utilizes the glutamate gene information provided by abagen (available from: https://doi.org/10.5281/zenodo.3451463) toolbox (Markello et al., 2021) to enrich the functional connectivity analysis in brain aging during movie watching. The Allen Human Brain Atlas (AHBA) dataset (French and Paus, 2015; Hawrylycz et al., 2012) provides expression data for more than 20,000 genes across 3702 brain areas in MRI-derived stereotactic space, which includes the glutamate genes GLUD1 and GLUD2 (Markello et al., 2021).
Methods:
The movie-watching functional magnetic resonance imaging (fMRI) dataset was collected from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN, http://www.cam-can.org/) (Taylor et al., 2017). All fMRI images (Older:185, younger:198) were preprocessed using SPM as implemented in the Neuroscience Information Toolbox (http://www.neuro.uestc.edu.cn/NIT.html) (Dong et al., 2018). The data preprocessing pipeline is as follows: 1) deleting the first 5 scans; 2) realignment and slice time correction. 3) spatial normalization and smoothing. 4) regressing out nuisance covariates. 5) temporally filtering. The GLUD1 and GLUD2 genes were used to enrich the movie-watching fMRI by applying Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) (Dipasquale et al., 2019). Next, these glutamate gene-enriched connectivity maps of the older and younger were compared using two sample T-test. Statistical analyses were performed with false discovery rate correction (p<0.05, FDR corrected). Additionally, we aimed to determine whether the effects of aging are more pronounced in specific functional brain networks by performing a network enrichment analysis (a spin-based spatial permutation test) (Baller et al., 2022).
Results:
Several cortical networks are involved in the effect of aging on FCs in the glutamate gene-enriched maps. For the GLUD1 gene, compared to young group (p<0.05, FDR corrected), FCs significantly decreased in the default network and the temporal parietal network as well as in the ventral attention network in the older group during movie watching. The proportion of the default network B and C is 2.9% and 1.3% respectively. Meanwhile, FCs in the older group increased in the limbic network and control network. As for GLUD2 gene, network analysis revealed that age-related increases in glutamate gene-enriched FCs were most pronounced in the default A network, the control A network, and the limbic A network. FCs significantly decrease in dorsal attention B network, ventral attention B network, control B network and default B network. More details can be found in Figure 1.
Conclusions:
In conclusion, our results showed that during movie-watching, glutamate gene- enriched FCs which related to aging mainly increased in the limbic and control networks as well as default A network in the older. The reduction is mainly in the ventral attention network and default network. The glutamate gene-enriched FCs during movie watching may offer valuable insights into the molecular mechanisms of brain aging.
Genetics:
Genetic Association Studies 2
Lifespan Development:
Aging 1
Keywords:
Aging
FUNCTIONAL MRI
Glutamate
Other - Movie-watching
1|2Indicates the priority used for review
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