title: Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease.
abstract: Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimer's disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3×Tg)-AD model mice. Five- to seven-month-old 3×Tg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3×Tg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3×Tg-AD mice. However, 28 days after TBI, the 3×Tg-AD mice exhibited significantly lower spatial learning than the sham-treated 3×Tg-AD mice. Correspondingly, while a few amyloid-β (Aβ) plaques were observed in both sham-treated and TBI-treated 3×Tg-AD mouse hippocampus 7 days after TBI, the Aβ deposition was significantly greater in 3×Tg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal Aβ deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3×Tg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved.
authors.affiliation: Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Shishido
authors.affiliation: Laboratory of Biophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Japan. Electronic address: kishimot@kph.bunri-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kishimoto
authors.affiliation: Department of Neurological Surgery Kagawa General Rehabilitation Hospital, Japan. Electronic address: nobu@kagawa-reha.net.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawai
authors.affiliation: Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Toyota
authors.affiliation: Department of Inflammation Pathology, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Laboratory of Biophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Laboratory of Biophysics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kirino
authors.affiliation: Department of Neurological Surgery, Faculty of Medicine, Kagawa University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D060825:Cognitive Dysfunction / Q000150:complications; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D065853:Spatial Learning
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer’s disease; Amyloid-β protein; Cognitive impairment; Traumatic brain injury; Triple-transgenic AD-model mouse