Comparing Differential Gene Expression in Chronic Traumatic Encephalopathy, Parkinson's Disease, and Bipolar Disorder

Main Article Content

Francia Victoria De Los Reyes
Carina Villamayor

Abstract

Introduction. Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is
defined, neuropathologically, by the presence of aggregated hyperphosphorylated tau in the neurons and
astrocytes of the perivascular area that is located deep in the cerebral sulci. The lesion is associated with
repetitive brain trauma, from the spectrum of asymptomatic subconcussive head injury to grossly identifiable
features of concussion. Although the diagnostic neuropathology of CTE is well-characterized, the precise
mechanism that causes this to occur in CTE is not yet clearly elucidated. The features of hyperphosphorylated
tau in CTE is quite similar with Alzheimer’s Disease (AD), as is the reduced expression of certain genes that
are required to dephosphorylate tau, which is the putative culprit in the generation of amyloid aggregates
and hyperphosphorylated tau.1 In comparison, Parkinson’s Disease (PD) is a neurodegenerative disease that
is caused by accumulation of misfolded alpha-synuclein (α-syn) that causes the formation of intraneuronal
Lewy Body aggregates. The pattern of accumulation for α-syn involves the olfactory bulb and the gut with
progressive involvement of the posterior part of the brain.2 Despite establishing the presence of two different
intraneuronal inclusions for CTE and PD, contact sports associated with the clinical spectrum of CTE has been
shown to present with Parkinsonian features along with dementia. Mood disorders has been reported to occur
in patients with these neurologic conditions. Several studies have documented that patients had a previous
experience of traumatic brain injury prior to the diagnosis of Bipolar Disorder (BD). A review of electronic
literature suggested that having an earlier diagnosis of BD increased the likelihood of having a diagnosis of
PD in the future.3,4


Objectives. This research aimed to compare the over- and underexpressed genes in cases with Parkinson's
Disease (PD), cases with Bipolar Disorder (BD), and cases with Chronic Traumatic Encephalopathy (CTE) versus
normal controls. This was done to determine if parallel overexpression in certain genes may indicate the possible association at the level of gene expression. Identifying similar RNA sequence establishing gene expression may provide an insight to the relationship of the diseases in terms of pathobiological behavior. Determining the similar over- or underexpression pattern may provide an insight on the common pathobiologic mechanisms that may be the reason for the three disorders being associated by way of pre-morbid or co-morbid condition.


Methodology. Transcripts from the public domain archive of the NCBI SRA were identified for the RNA sequence (RNAseq) of interest using the search string “Chronic Traumatic Encephalopathy,” “Bipolar Disorder,” and “Parkinson.” Only public domain transcriptome files of post-mortem brain samples labeled as RNAseq data
extracted thru the Illumina platform that have a paired normal control were selected. A total of ten (10)
cases for each disorder and thirty (30) normal subjects for control in the NCBI SRA RNAseq database with
a whole exome sequence file that was available for public domain use was utilized for differential gene
expression analysis.6,7,8


Results and Discussion. Among 21,122 identified genes from the RNAseq, the analysis was able to identify
26 genes exhibiting increased expression of up to >15 log2 fold change among cases with CTE, PD, and
BD compared with normal controls. In contradistinction, only 6 well-described genes exhibited a decreased
expression among cases with CTE and BD compared to normal controls. However, there were no identified genes that exhibited underexpression in cases with PD compared with normal controls. The identification of parallel gene overexpression among the CTE, BD, and PD groups with respect to structural integrity, cellular metabolism, homeostasis, and apoptosis may indicate a common pathway that have been initiated as part of the response to maintain tissue function or as a consequence of the underlying pathobiologic mechanism that caused the primary lesion.

Article Details

How to Cite
De Los Reyes, F. V., & Villamayor, C. (2020). Comparing Differential Gene Expression in Chronic Traumatic Encephalopathy, Parkinson’s Disease, and Bipolar Disorder. Philippine Journal of Pathology, 5(1). Retrieved from https://philippinejournalofpathology.org/index.php/PJP/article/view/177
Section
Original Articles
Author Biographies

Francia Victoria De Los Reyes, University of the East Ramon Magsaysay Memorial Medical Center, Quezon City

Graduate, AP/CP Residency Training Program, Department of Pathology and Pathology Laboratory 

Carina Villamayor, University of the East Ramon Magsaysay Memorial Medical Center, Quezon City

Chairperson, Department of Pathology

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