TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease

Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer’s disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristi...

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Main Authors: Hunter White, Ryan Webb, Ian McKnight, Kaitlyn Legg, Chan Lee, Peter H.U. Lee, Olivia Smith Spicer, Joon W. Shim
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.936151/full
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author Hunter White
Ryan Webb
Ian McKnight
Kaitlyn Legg
Chan Lee
Peter H.U. Lee
Peter H.U. Lee
Olivia Smith Spicer
Joon W. Shim
author_facet Hunter White
Ryan Webb
Ian McKnight
Kaitlyn Legg
Chan Lee
Peter H.U. Lee
Peter H.U. Lee
Olivia Smith Spicer
Joon W. Shim
author_sort Hunter White
collection DOAJ
description Symptoms of normal pressure hydrocephalus (NPH) and Alzheimer’s disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristics consistent throughout species is poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and amyloid precursor protein (APP). Using the genome data viewer, we analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of six genes of interest and one house keeping gene with two factors associated with high mutation rate: 1) proximity to telomeres or 2) high adenine and thymine (A + T) content. We found that TRPV4 and microtubule associated protein tau (MAPT) mRNA were elevated in NPH. In AD, mRNA expression of TRPV4 was unaltered unlike APP and other genes. In mice, rats, and humans, the nucleotide size of TRPV4 did not vary, while in other genes, the sizes were inconsistent. Proximity to telomeres in TRPV4 was <50 Mb across species. Our analyses reveal that TRPV4 gene size and mutability are conserved across three species, suggesting that TRPV4 can be a potential link in the pathophysiology of chronic hydrocephalus in aged humans (>65 years) and laboratory rodents at comparable ages.
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spelling doaj.art-14078c97b4004bf1b684871a41ae11b12022-12-22T03:29:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.936151936151TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s diseaseHunter White0Ryan Webb1Ian McKnight2Kaitlyn Legg3Chan Lee4Peter H.U. Lee5Peter H.U. Lee6Olivia Smith Spicer7Joon W. Shim8Department of Biomedical Engineering, Marshall University, Huntington, WV, United StatesDepartment of Biomedical Engineering, Marshall University, Huntington, WV, United StatesDepartment of Biomedical Engineering, Marshall University, Huntington, WV, United StatesDepartment of Biomedical Engineering, Marshall University, Huntington, WV, United StatesDepartment of Anesthesia, Indiana University Health Arnett Hospital, Lafayette, IN, United StatesDepartment of Cardiothoracic Surgery, Southcoast Health, Fall River, MA, United StatesDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, United StatesNational Institute of Mental Health, National Institute of Health, Bethesda, MD, United StatesDepartment of Biomedical Engineering, Marshall University, Huntington, WV, United StatesSymptoms of normal pressure hydrocephalus (NPH) and Alzheimer’s disease (AD) are somewhat similar, and it is common to misdiagnose these two conditions. Although there are fluid markers detectable in humans with NPH and AD, determining which biomarker is optimal in representing genetic characteristics consistent throughout species is poorly understood. Here, we hypothesize that NPH can be differentiated from AD with mRNA biomarkers of unvaried proximity to telomeres. We examined human caudate nucleus tissue samples for the expression of transient receptor potential cation channel subfamily V member 4 (TRPV4) and amyloid precursor protein (APP). Using the genome data viewer, we analyzed the mutability of TRPV4 and other genes in mice, rats, and humans through matching nucleotides of six genes of interest and one house keeping gene with two factors associated with high mutation rate: 1) proximity to telomeres or 2) high adenine and thymine (A + T) content. We found that TRPV4 and microtubule associated protein tau (MAPT) mRNA were elevated in NPH. In AD, mRNA expression of TRPV4 was unaltered unlike APP and other genes. In mice, rats, and humans, the nucleotide size of TRPV4 did not vary, while in other genes, the sizes were inconsistent. Proximity to telomeres in TRPV4 was <50 Mb across species. Our analyses reveal that TRPV4 gene size and mutability are conserved across three species, suggesting that TRPV4 can be a potential link in the pathophysiology of chronic hydrocephalus in aged humans (>65 years) and laboratory rodents at comparable ages.https://www.frontiersin.org/articles/10.3389/fgene.2022.936151/fullMRNA markerTRPV4MAPTnormal pressure hydrocephalusAlzheimer’s disease
spellingShingle Hunter White
Ryan Webb
Ian McKnight
Kaitlyn Legg
Chan Lee
Peter H.U. Lee
Peter H.U. Lee
Olivia Smith Spicer
Joon W. Shim
TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
Frontiers in Genetics
MRNA marker
TRPV4
MAPT
normal pressure hydrocephalus
Alzheimer’s disease
title TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
title_full TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
title_fullStr TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
title_full_unstemmed TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
title_short TRPV4 mRNA is elevated in the caudate nucleus with NPH but not in Alzheimer’s disease
title_sort trpv4 mrna is elevated in the caudate nucleus with nph but not in alzheimer s disease
topic MRNA marker
TRPV4
MAPT
normal pressure hydrocephalus
Alzheimer’s disease
url https://www.frontiersin.org/articles/10.3389/fgene.2022.936151/full
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