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Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury
James A. Haley Veteran's Administration Hospital, Tampa, FL 33612, USA
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USA
Department of Biophysics, School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024, China
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USA
* Author to whom correspondence should be addressed.
Received: 29 October 2013; in revised form: 3 January 2014 / Accepted: 6 January 2014 / Published: 9 January 2014
Abstract: Traumatic brain injury (TBI) occurs in response to an acute insult to the head and is recognized as a major risk factor for Alzheimer’s disease (AD). Indeed, recent studies have suggested a pathological overlap between TBI and AD, with both conditions exhibiting amyloid-beta (Aβ) deposits, tauopathy, and neuroinflammation. Additional studies involving animal models of AD indicate that some AD-related genotypic determinants may be critical factors enhancing temporal and phenotypic symptoms of TBI. Thus in the present study, we examined sub-acute effects of moderate TBI delivered by a gas-driven shock tube device in Aβ depositing Tg2576 mice. Three days later, significant increases in b-amyloid deposition, glycogen synthase-3 (GSK-3) activation, phospho-tau, and pro-inflammatory cytokines were observed. Importantly, peripheral treatment with the naturally occurring flavonoid, luteolin, significantly abolished these accelerated pathologies. This study lays the groundwork for a safe and natural compound that could prevent or treat TBI with minimal or no deleterious side effects in combat personnel and others at risk or who have experienced TBI.
Keywords: traumatic brain injury; Alzheimer’s disease; amyloidogenesis; tauopathy; GSK; neuroinflammation; luteolin
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MDPI and ACS Style
Sawmiller, D.; Li, S.; Shahaduzzaman, M.; Smith, A.J.; Obregon, D.; Giunta, B.; Borlongan, C.V.; Sanberg, P.R.; Tan, J. Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury. Int. J. Mol. Sci. 2014, 15, 895-904.
Sawmiller D, Li S, Shahaduzzaman M, Smith AJ, Obregon D, Giunta B, Borlongan CV, Sanberg PR, Tan J. Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury. International Journal of Molecular Sciences. 2014; 15(1):895-904.
Sawmiller, Darrell; Li, Song; Shahaduzzaman, Md; Smith, Adam J.; Obregon, Demian; Giunta, Brian; Borlongan, Cesar V.; Sanberg, Paul R.; Tan, Jun. 2014. "Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury." Int. J. Mol. Sci. 15, no. 1: 895-904.