Association between gene expression and altered resting-state functional networks in type 2 diabetes

• Published in: Frontiers in aging neuroscience 2023-11, Vol.15, p.1290231-1290231
• Main Authors: Zhang, Yang, Du, Xin, Qin, Wen, Fu, Yumeng, Wang, Zirui, Zhang, Quan
• Format: Article
• Language: English
• Subjects: Aging Neuroscience; Allen human brain atlas; Brain; Brain mapping; Cognitive ability; Cortex (parietal); Dementia; Diabetes; Diabetes mellitus (non-insulin dependent); Disease; functional connectivity; Functional magnetic resonance imaging; Gene expression; independent component analysis; Medical imaging; Metabolic disorders; Neural networks; Neuroimaging; Oligodendrocyte-myelin glycoprotein; Peripheral neuropathy; Rac1 protein; Software; TrkB receptors; type 2 diabetes
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2023.1290231

Type 2 diabetes (T2DM) is a polygenic metabolic disorder that accelerates brain aging and harms cognitive function. The underlying mechanism of T2DM-related brain functional changes has not been clarified. Resting-fMRI data were obtained from 99 T2DM and 109 healthy controls (HCs). Resting-state functional connectivity networks (RSNs) were separated using the Independent Component Analysis (ICA) method, and functional connectivity (FC) differences between T2DM patients and HCs within the RSNs were detected. A partial least squares (PLS) regression was used to test the relation between gene expression from Allen Human Brain Atlas (AHBA) and intergroup FC differences within RSNs. Then the FC differences-related gene sets were enriched to determine the biological processes and pathways related to T2DM brain FC changes. The T2DM patients showed significantly increased FC in the left middle occipital gyrus (MOG) of the precuneus network (PCUN) and the right MOG / right precuneus of the dorsal attention network (DAN). FC differences within the PCUN were linked with the expression of genes enriched in the potassium channel and TrkB-Rac1 signaling pathways and biological processes related to synaptic function. This study linked FC and molecular alterations related to T2DM and suggested that the T2DM-related brain FC changes may have a genetic basis. This study hoped to provide a unique perspective to understand the biological substrates of T2DM-related brain changes.