Journal Article

Alterations of transcriptome signatures in head trauma-related neurodegenerative disorders

Shin, Jong-Yeon, Stein, Thor D., Ryu, Hoon, Lee, Junghee, Kowall, Neil W., Cho, Hyesun, Seo, Jeong-Sun, Hyeon, Seung Jae, Alvarez, Victor E., McKee, Ann C.

2020

Overview

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is associated with repetitive traumatic brain injury (TBI). CTE is known to share similar neuropathological features with Alzheimer’s disease (AD), but little is known about the molecular properties in CTE. To better understand the neuropathological mechanism of TBI-related disorders, we conducted transcriptome sequencing analysis of CTE including AD and CTE with AD (CTE/AD) post-mortem human brain samples. Through weighted gene co-expression network analysis (WGCNA) and principal component analysis (PCA), we characterized common and unique transcriptome signatures among CTE, CTE/AD, and AD. Interestingly, synapse signaling-associated gene signatures (such as synaptotagmins) were commonly down-regulated in CTE, CTE/AD, and AD. Quantitative real-time PCR (qPCR) and Western blot analyses confirmed that the levels of synaptotagmin 1 (SYT1) were markedly decreased in CTE and AD compared to normal. In addition, calcium/calmodulin-dependent protein kinase II (CaMKII), protein kinase A (PKA), protein kinase C (PKC), and AMPA receptor genes that play a pivotal role in memory function, were down-regulated in head trauma-related disorders. On the other hand, up-regulation of cell adhesion molecules (CAMs) associated genes was only found in CTE. Our results indicate that dysregulation of synaptic transmission- and memory function-related genes are closely linked to the pathology of head injury-related disorder and AD. Alteration of CAMs-related genes may be specific pathological markers for the CTE pathology.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38 / 38/39 / 38/91 / 631/208/199 / 631/378/2591/2592 / 631/378/548/1964 / 64 / 82 / 82/51 / Aged / Aged, 80 and over / Alzheimer Disease - complications / Alzheimer Disease - genetics / Alzheimer's disease / Autopsy / Blotting, Western / Ca2+/calmodulin-dependent protein kinase II / Calcium-binding protein / Calmodulin / Cell adhesion & migration / Cell adhesion molecules / Cell Adhesion Molecules - biosynthesis / Cell Adhesion Molecules - genetics / Chronic traumatic encephalopathy / Chronic Traumatic Encephalopathy - complications / Chronic Traumatic Encephalopathy - genetics / Chronic Traumatic Encephalopathy - pathology / Craniocerebral Trauma - complications / Endothelial Cells - metabolism / Female / Gene expression / Gene Ontology / Gene Regulatory Networks / Genes / Head injuries / Humanities and Social Sciences / Humans / Kinases / Male / Memory / Middle Aged / multidisciplinary / Nerve Tissue Proteins - biosynthesis / Nerve Tissue Proteins - genetics / Neurodegenerative diseases / Neuroglia - metabolism / Neurons - metabolism / Neuropathology / Pathology / Principal components analysis / Protein kinase A / Protein kinase C / Proteins / Real-Time Polymerase Chain Reaction / Science / Science (multidisciplinary) / Sequence analysis / Sequence Analysis, RNA / Synapses / Synaptic transmission / Synaptic Transmission - genetics / Synaptotagmin / Temporal Lobe - metabolism / Temporal Lobe - pathology / Transcription, Genetic / Transcriptome / Trauma / Traumatic brain injury / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid / α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors