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Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease.

Abstract

This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels. Trehalose treatment significantly improved performance in the Morris water maze, consistent with enhanced learning and memory. The improvement was not associated with significant modulation of full length amyloid-β protein precursor or other amyloid-β fragments. Trehalose had no effect on autophagy as assessed by western blot of the LC3-1 to LC3-2 protein ratio, and no alteration in biometals that might account for the improved cognition was observed. Biochemical analysis revealed a significant increase in the hippocampus of both synaptophysin, a synaptic vesicle protein and surrogate marker of synapses, and doublecortin, a reliable marker of neurogenesis. The growth factor progranulin was also significantly increased in the hippocampus and cortex with trehalose treatment. This study suggests that trehalose might invoke a suite of neuroprotective mechanisms that can contribute to improved cognitive performance in AD that are independent of more classical trehalose-mediated pathways, such as Aβ reduction and activation of autophagy. Thus, trehalose may have utility as a potential AD therapeutic, with conceivable implications for the treatment of other neurodegenerative disorders.

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  • Authors+Show Affiliations

    ,

    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

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    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia. University of Technology Sydney, Elemental Bio-imaging, Broadway, Australia.

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    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

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    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

    ,

    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

    ,

    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

    The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, The University of Melbourne, Parkville, VIC, Australia.

    Source

    MeSH

    Alzheimer Disease
    Amyloid beta-Protein Precursor
    Animals
    Brain
    Cognition Disorders
    Disease Models, Animal
    Green Fluorescent Proteins
    Humans
    Laser Therapy
    Mass Spectrometry
    Maze Learning
    Metals
    Mice
    Mice, Transgenic
    Microtubule-Associated Proteins
    Neuroprotective Agents
    Presenilin-1
    Recombinant Fusion Proteins
    Trehalose

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28869469

    Citation

    Portbury, Stuart D., et al. "Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 60, no. 2, 2017, pp. 549-560.
    Portbury SD, Hare DJ, Sgambelloni C, et al. Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2017;60(2):549-560.
    Portbury, S. D., Hare, D. J., Sgambelloni, C., Perronnes, K., Portbury, A. J., Finkelstein, D. I., & Adlard, P. A. (2017). Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 60(2), pp. 549-560. doi:10.3233/JAD-170322.
    Portbury SD, et al. Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2017;60(2):549-560. PubMed PMID: 28869469.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. AU - Portbury,Stuart D, AU - Hare,Dominic J, AU - Sgambelloni,Charlotte, AU - Perronnes,Kali, AU - Portbury,Ashley J, AU - Finkelstein,David I, AU - Adlard,Paul A, PY - 2017/9/5/pubmed PY - 2018/4/10/medline PY - 2017/9/5/entrez KW - Alzheimer’s disease KW - Tg2576 KW - progranulin KW - synaptophysin KW - trehalose SP - 549 EP - 560 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 60 IS - 2 N2 - This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels. Trehalose treatment significantly improved performance in the Morris water maze, consistent with enhanced learning and memory. The improvement was not associated with significant modulation of full length amyloid-β protein precursor or other amyloid-β fragments. Trehalose had no effect on autophagy as assessed by western blot of the LC3-1 to LC3-2 protein ratio, and no alteration in biometals that might account for the improved cognition was observed. Biochemical analysis revealed a significant increase in the hippocampus of both synaptophysin, a synaptic vesicle protein and surrogate marker of synapses, and doublecortin, a reliable marker of neurogenesis. The growth factor progranulin was also significantly increased in the hippocampus and cortex with trehalose treatment. This study suggests that trehalose might invoke a suite of neuroprotective mechanisms that can contribute to improved cognitive performance in AD that are independent of more classical trehalose-mediated pathways, such as Aβ reduction and activation of autophagy. Thus, trehalose may have utility as a potential AD therapeutic, with conceivable implications for the treatment of other neurodegenerative disorders. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/28869469/Trehalose_Improves_Cognition_in_the_Transgenic_Tg2576_Mouse_Model_of_Alzheimer's_Disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-170322 DB - PRIME DP - Unbound Medicine ER -