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Alterations of transcriptome signatures in head trauma-related neurodegenerative disorders
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
- Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Male
Transcription, Genetic
Blotting, Western
lcsh:Medicine
Nerve Tissue Proteins
AMPA receptor
Biology
SYT1
Real-Time Polymerase Chain Reaction
Synaptic Transmission
Article
Chronic Traumatic Encephalopathy
Transcriptome
Alzheimer Disease
Memory
Ca2+/calmodulin-dependent protein kinase
medicine
Craniocerebral Trauma
Humans
Gene Regulatory Networks
Protein kinase A
lcsh:Science
Protein kinase C
Aged
Aged, 80 and over
Neurons
Multidisciplinary
Sequence Analysis, RNA
lcsh:R
Endothelial Cells
Human brain
Neurotransmitters
Middle Aged
medicine.disease
Temporal Lobe
Chronic traumatic encephalopathy
medicine.anatomical_structure
Gene Ontology
Cancer research
Long-term potentiation
lcsh:Q
Female
Gene expression
Cell Adhesion Molecules
Neuroglia
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....256c7255be63ef98087bf79df37c0ddf