title: Decreased level of olfactory receptors in blood cells following traumatic brain injury and potential association with tauopathy.
abstract: Traumatic brain injury (TBI) is a leading cause of death and disability among children and young adults in the United States. In this study, we explored whether changes in the gene expression profile of peripheral blood mononuclear cells (PBMC) may provide a clinically assessable "window" into the brain, reflecting molecular alterations following TBI that might contribute to the onset and progression of TBI clinical complications. We identified three olfactory receptor (OR) TBI biomarkers that are aberrantly down-regulated in PBMC specimens from TBI subjects. Down-regulation of these OR biomarkers in PBMC was correlated with the severity of brain injury and TBI-specific symptoms. A two- biomarker panel comprised of OR11H1 and OR4M1 provided the best criterion for segregating the TBI and control cases with 90% accuracy, 83.3% sensitivity, and 100% specificity. We found that the OR biomarkers are ectopically expressed in multiple brain regions, including the entorhinal-hippocampus system known to play an important role in memory formation and consolidation. Activation of OR4M1 led to attenuation of abnormal tau phosphorylation, possibly through JNK signaling pathway. Our results suggested that addition of the two-OR biomarker model to current diagnostic criteria may lead to improved TBI detection for clinical trials, and decreased expression of OR TBI biomarkers might be associated with TBI-induced tauopathy. Future studies exploring the physiological relevance of OR TBI biomarkers in the normal brain and in the brain following TBI will provide a better understanding of the biological mechanisms underlying TBI and insights into novel therapeutic targets for TBI.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Merina
authors.initials: M
authors.lastname: Varghese
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.|GRECC, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA.
authors.forename: Shrishailam
authors.initials: S
authors.lastname: Yemul
authors.affiliation: Department of Rehabilitation, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Dams-O'Connor
authors.affiliation: Department of Rehabilitation, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Gordon
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Knable
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Freire
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.|Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.|GRECC, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA.
authors.forename: Giulio Maria
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D015331:Cohort Studies; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018035:Receptors, Odorant / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D024801:Tauopathies / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018035:Receptors, Odorant