Traumatic Brain Injury by Weight-Drop Method Causes Transient Amyloid-β Deposition and Acute Cognitive Deficits in Mice.

Hajime Shishido,Yutaka Kirino,Yasunori Toyota,Takashi Tamiya,Masahisa Matsumura,Nobuyuki Kawai,Yasushi Kishimoto,Kana Sato,Masaki Ueno

doi:10.1155/2019/3248519

Hajime Shishido, Yutaka Kirino + Show 7 more

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https://doi.org/10.1155/2019/3248519

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Abstract

There has been growing awareness of the correlation between an episode of traumatic brain injury (TBI) and the development of Alzheimer's disease (AD) later in life. It has been reported that TBI accelerated amyloid-β (Aβ) pathology and cognitive decline in the several lines of AD model mice. However, the short-term and long-term effects of TBI by the weight-drop method on amyloid-β pathology and cognitive performance are unclear in wild-type (WT) mice. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in wild-type C57BL6J mice. Five- to seven-month-old WT mice were subjected to either TBI by the weight-drop method or a sham treatment. Seven days after TBI, the WT mice exhibited significantly lower spatial learning than the sham-treated WT mice. However, 28 days after TBI, the cognitive impairment in the TBI-treated WT mice recovered. Correspondingly, while significant amyloid-β (Aβ) plaques and amyloid precursor protein (APP) accumulation were observed in the TBI-treated mouse hippocampus 7 days after TBI, the Aβ deposition was no longer apparent 28 days after TBI. Thus, TBI induced transient amyloid-β deposition and acute cognitive impairments in the WT mice. The present study suggests that the TBI could be a risk factor for acute cognitive impairment even when genetic and hereditary predispositions are not involved. The system might be useful for evaluating and developing a pharmacological treatment for the acute cognitive deficits.

Highlights

Traumatic brain injury (TBI) occurs when an external force transmitted to the head results in short- and/or long-term cognitive disability [1]
The latency to reach the site where the platform had been placed was significantly longer in TBI-treated mice than in control mice (Figure 1(a), p < 0 05), and the percentage of time spent in the target quadrant (T) was significantly less in TBI-treated mice (Figure 1(b), p = 0 024)
In order to examine the visual and motor deficits in TBI-treated mice, the mice were allowed to run in the visible platform version of the Morris Water Maze (MWM)

Summary

Introduction

Traumatic brain injury (TBI) occurs when an external force transmitted to the head results in short- and/or long-term cognitive disability [1]. To elucidate the molecular mechanism by which TBI increases the risk of AD, several studies using mouse models of AD have been performed [8,9,10,11]. Most of these studies have found evidence that TBI accelerated the onset of AD-related histopathological changes and cognitive impairment [8, 9]. We reported that TBI accelerated amyloid-β (Aβ) pathology and cognitive deficits in triple transgenic- (3×Tg-) AD model mice [12, 13]. We used the weight-drop method [14, 15], a closed head injury model, to mimic diffuse axonal injury (DAI)

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