Trehalose reduces nerve injury induced nociception in mice but negatively affects alertness

  • Trehalose, a sugar from fungi, mimics starvation due to a block of glucose transport and induces Transcription Factor EB- mediated autophagy, likely supported by the upregulation of progranulin. The pro-autophagy effects help to remove pathological proteins and thereby prevent neurodegenerative diseases such as Alzheimer’s disease. Enhancing autophagy also contributes to the resolution of neuropathic pain in mice. Therefore, we here assessed the effects of continuous trehalose administration via drinking water using the mouse Spared Nerve Injury model of neuropathic pain. Trehalose had no effect on drinking, feeding, voluntary wheel running, motor coordination, locomotion, and open field, elevated plus maze, and Barnes Maze behavior, showing that it was well tolerated. However, trehalose reduced nerve injury-evoked nociceptive mechanical and thermal hypersensitivity as compared to vehicle. Trehalose had no effect on calcium currents in primary somatosensory neurons, pointing to central mechanisms of the antinociceptive effects. In IntelliCages, trehalose-treated mice showed reduced activity, in particular, a low frequency of nosepokes, which was associated with a reduced proportion of correct trials and flat learning curves in place preference learning tasks. Mice failed to switch corner preferences and stuck to spontaneously preferred corners. The behavior in IntelliCages is suggestive of sedative effects as a 'side effect' of a continuous protracted trehalose treatment, leading to impairment of learning flexibility. Hence, trehalose diet supplements might reduce chronic pain but likely at the expense of alertness.

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Author:Vanessa Kraft, Katja Schmitz, Annett Wilken-Schmitz, Gerd GeisslingerORCiDGND, Marco SisignanoORCiDGND, Irmgard TegederORCiD
Parent Title (English):Nutrients
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/25
Date of first Publication:2021/08/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/09/22
Tag:IntelliCage; fungal sugar; learning and memory; nociception; spared nerve injury
Issue:9, art. 2953
Page Number:17
First Page:1
Last Page:17
The study was supported by the Deutsche Forschungsgemeinschaft (CRC1080, C02 to IT) and the research funding program 'Landesoffensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz' (LOEWE) of the State of Hessen, Research Center for Translational Medicine and Pharmacology, TMP, (to KS) and the Fraunhofer Cluster of Excellence for Immune Mediated diseases/CIMD) (to GG). The funding institution had no role in the conceptualization, design, data collection, analysis decision to publish, or preparation of the manuscript.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0