Page 83 - Q. Neuroscience

Repetitive head injury alters olfactory-associated
electroencephalographic, behavioral, and pathological sequelae in mice
1,3
Younghyun Yoon 1,2* , YunHee Seol , Hyoenjoo Im , Hio-Been Han , Jeongeun Kum ,
3*
3*
1,4
Jee Hyun Choi 1,4# & Hoon Ryu 1,5#
1 Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, ROK; 2 Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, 37235, USA; 3 Program of Brain and Cognitive
Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, ROK; 4 Department of Neuroscience, Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 027
92, ROK; 5 Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA 02130, USA
Abstract Introduction
A series of repeated mild traumatic brain injury (TBI) by collision sports
or accidents lead to long-term cognitive impairments with an increased Olfactory Dysfunction is commonly reported in TBI patients and
risk for neurodegenerative and psychiatric disorders. Olfactory animal models.
dysfunction has been observed as one of the most prominent symptoms • Olfaction is one of the primary sensory perceptions responsible
in TBI patients, but the exact pathological mechanism is not fully
understood. In this present study, we investigated the acute effects of for memory and emotions
repetitive mild TBI (r-mTBI) on olfactory functioning and its pathological • a-synuclein and tauopathy changes in the olfactory system are
neuronal injuries using a TBI mouse model that mimics concussions in indicators of dementia risk.
humans. Electroencephalography (EEG) neural impairments observed
in the olfactory bulb revealed significantly attenuated modulation index
values for delta-phase fast oscillations. As well as significantly reduced Aims of Study
cross-frequency couplings between delta phase and beta/low gamma
amplitudes in concussed mice. Then, through pathological examination,
we found a significant increase in p-Tau (S202/T205) in olfactory bulb- Hypothesis: Olfactory dysfunction may be an indicator
associated areas. Furthermore, neuronal atrophy was correlated with p- of cognitive decline in mice exposed to repetitive-mild
Tau levels. Lastly, TBI mice showed for an abnormal loss of preference TBI events.
in home bedding under Y-maze conditions compared to controls.
Together, p-Tau alterations may serve as important biomarkers of Aim 1: To develop a new TBI mouse model that closely
olfactory track-associated dysfunctions and behavioral impairments. resembles human sub-concussion scenarios.
KEY WORDS: Traumatic Brain Injury, Olfactory System, EEG, Tau, Aim 2: To investigate the pathological detriments in the
neuronal atrophy olfactory system after r-mTBI events.

RESULTS

1. EEG phase attenuation in the olfactory bulb 2. r-mTBI increases tauopathy in olfactory bulb associated areas

3. Tauopathy is correlated with neuronal atrophy in OB associated areas 4. Preference for home bedding is lost

Conclusion
Conclusion:
R-mTBI is associated with increased tauopathy, decreased cell size, and impairments in
neural oscillations in the mouse Olfactory system. Together, the magnitude of structural
and functional impairments underlying olfaction in r-mTBI models may serve as an
activator of cognitive decline and dementia risk.

Acknowledgements:
This research was supported by the Brain Research Program through Korean National Research Foundation
(NRF-2016M3C7A1904233, NRF-2018M3C7A1056894, NRF-2020M3E5D9079742), and the grant from
Korea Institute of Science and Technology (2E30320).