Increases of phospho-Tau (Ser202/Thr205) in the olfactory regions are associated with impaired EEG and olfactory behavior in traumatic brain injury mice

Abstract

Traumatic brain injury (TBI) leads to long-term cognitive impairments with an increased risk for neurodegenerative and psychiatric disorders. Among these various impairments, olfactory dysfunction is one of the most common symptoms in TBI patients. However, there are very few studies that show the association between olfactory dysfunction and repetitive TBI, which accounts for the majority of all head injuries. In this present study, we investigated the effects of repetitive TBI on olfactory functioning and the related pathological neuronal injuries in mice. Through pathological examination, we found a significant increase in p-Tau (S202/T205) in olfactory bulb-associated areas such as the Anterior Olfactory Nucleus (AON), Pyriform Cortex (PC), Tenia Tecta (TT), and Olfactory Tubercle (OT). Neuronal atrophy in the Lateral Anterior Olfactory Nucleus (AOL), Granule Layer Olfactory Bulb (GrO), and Dorsal Tenia Tecta (DTT) was also found to be correlated with p-Tau levels. Furthermore, electroencephalography (EEG) of repetitive TBI mouse models showed impaired spontaneous delta oscillation, as well as altered cross-frequency coupling between delta phase and amplitudes of the fast oscillations in the resting-state olfactory bulb. Also, abnormal alterations in EEG band powers were observed during the olfactory oddball paradigm test. This study provides evidence of pathological and physiological alterations in the mouse olfactory system caused by repetitive TBI. Together, p-Tau alterations and EEG impairments may serve as important biomarkers of olfactory track-associated dysfunctions and behavioral impairments commonly observed in repetitive TBI patients.