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2017-08-25 19:45:37 UTC
Trehalose improves traumatic brain injury-induced cognitive impairment
Stuart D. Portbury, Dominic J. Hare, David I. Finkelstein, Paul A. Adlard
PLOS x
Published: August 24, 2017
RESEARCH ARTICLE
https://doi.org/10.1371/journal.pone.0183683
Abstract
Traumatic brain Injury (TBI) is a significant cause of death and long-term disability for which there are currently no effective pharmacological treatment options. In this study then, we utilized a mouse model of TBI to assess the therapeutic potential of the stable disaccharide trehalose, which is known to protect against oxidative stress, increase levels of chaperone molecules and enhance autophagy. Furthermore, trehalose has demonstrated neuroprotective properties in numerous animal models and has been proposed as a potential treatment for neurodegeneration. As TBI (and associated neurodegenerative disorders) is complicated by a sudden and dramatic change in brain metal concentrations, including iron (Fe) and zinc (Zn), the collective accumulation and translocation of which has been hypothesized to contribute to the pathogenesis of TBI, then we also sought to determine whether trehalose modulated the metal dyshomeostasis associated with TBI. In this study three-month-old C57Bl/6 wildtype mice received a controlled cortical impact TBI, and were subsequently treated for one month with trehalose. During this time animals were assessed on multiple behavioral tasks prior to tissue collection. Results showed an overall significant improvement in the Morris water maze, Y-maze and open field behavioral tests in trehalose-treated mice when compared to controls. These functional benefits occurred in the absence of any change in lesion volume or any significant modulation of biometals, as assessed by laser ablation inductively coupled plasma mass spectrometry. Western blot analysis, however, revealed an upregulation of synaptophysin, doublecortin and brain derived neurotrophic factor protein in trehalose treated mice in the contralateral cortex. These results indicate that trehalose may be efficacious in improving functional outcomes following TBI by a previously undescribed mechanism of action that has relevance to multiple disorders of the central nervous system.
Citation: Portbury SD, Hare DJ, Finkelstein DI, Adlard PA (2017) Trehalose improves traumatic brain injury-induced cognitive impairment. PLoS ONE 12(8): e0183683. https://doi.org/10.1371/journal.pone.0183683
Editor: Stephan N. Witt, Louisiana State University Health Sciences Center, UNITED STATES
Received: June 7, 2017; Accepted: August 9, 2017; Published: August 24, 2017
Copyright: © 2017 Portbury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper.
Funding: P.A.A. is supported by an Australian Research Council Future Fellowship (FT120100030). D.J.H. is supported by an Australian Research Council Linkage Project with Agilent Technologies (LP140100095).
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Stuart D. Portbury, Dominic J. Hare, David I. Finkelstein, Paul A. Adlard
PLOS x
Published: August 24, 2017
RESEARCH ARTICLE
https://doi.org/10.1371/journal.pone.0183683
Abstract
Traumatic brain Injury (TBI) is a significant cause of death and long-term disability for which there are currently no effective pharmacological treatment options. In this study then, we utilized a mouse model of TBI to assess the therapeutic potential of the stable disaccharide trehalose, which is known to protect against oxidative stress, increase levels of chaperone molecules and enhance autophagy. Furthermore, trehalose has demonstrated neuroprotective properties in numerous animal models and has been proposed as a potential treatment for neurodegeneration. As TBI (and associated neurodegenerative disorders) is complicated by a sudden and dramatic change in brain metal concentrations, including iron (Fe) and zinc (Zn), the collective accumulation and translocation of which has been hypothesized to contribute to the pathogenesis of TBI, then we also sought to determine whether trehalose modulated the metal dyshomeostasis associated with TBI. In this study three-month-old C57Bl/6 wildtype mice received a controlled cortical impact TBI, and were subsequently treated for one month with trehalose. During this time animals were assessed on multiple behavioral tasks prior to tissue collection. Results showed an overall significant improvement in the Morris water maze, Y-maze and open field behavioral tests in trehalose-treated mice when compared to controls. These functional benefits occurred in the absence of any change in lesion volume or any significant modulation of biometals, as assessed by laser ablation inductively coupled plasma mass spectrometry. Western blot analysis, however, revealed an upregulation of synaptophysin, doublecortin and brain derived neurotrophic factor protein in trehalose treated mice in the contralateral cortex. These results indicate that trehalose may be efficacious in improving functional outcomes following TBI by a previously undescribed mechanism of action that has relevance to multiple disorders of the central nervous system.
Citation: Portbury SD, Hare DJ, Finkelstein DI, Adlard PA (2017) Trehalose improves traumatic brain injury-induced cognitive impairment. PLoS ONE 12(8): e0183683. https://doi.org/10.1371/journal.pone.0183683
Editor: Stephan N. Witt, Louisiana State University Health Sciences Center, UNITED STATES
Received: June 7, 2017; Accepted: August 9, 2017; Published: August 24, 2017
Copyright: © 2017 Portbury et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper.
Funding: P.A.A. is supported by an Australian Research Council Future Fellowship (FT120100030). D.J.H. is supported by an Australian Research Council Linkage Project with Agilent Technologies (LP140100095).
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/634q5a
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk