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    Trehalose improves traumatic brain injury-induced cognitive impairment

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    14
    13
    Author
    Portbury, SD; Hare, DJ; Finkelstein, DI; Adlard, PA
    Date
    2017-08-24
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Finkelstein, David; Portbury, Stuart; Adlard, Paul; Hare, Dominic
    Affiliation
    Florey Department of Neuroscience and Mental Health
    School of BioSciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Portbury, S. D., Hare, D. J., Finkelstein, D. I. & Adlard, P. A. (2017). Trehalose improves traumatic brain injury-induced cognitive impairment. PLOS ONE, 12 (8), https://doi.org/10.1371/journal.pone.0183683.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254931
    DOI
    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.

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