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Akt phosphorylation is required for heat acclimation‐induced neuroprotection
Author(s) -
Shein Na’ama A.,
Tsenter Jeanna,
Alexandrovich Alexander G.,
Horowitz Michal,
Shohami Esther
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04862.x
Subject(s) - neuroprotection , protein kinase b , phosphorylation , pi3k/akt/mtor pathway , kinase , pharmacology , microbiology and biotechnology , biology , chemistry , medicine , signal transduction
Abstract Long‐term heat exposure, known as heat acclimation (HA; 30 days at 34 ± 1°C) is neuroprotective against traumatic brain injury. Acclimated mice were previously found to display improved functional recovery as well as an increase in the levels of the specific erythropoietin receptor. As the activation of this receptor is known to facilitate functional recovery on one hand and the phosphorylation and activation of Akt, an intracellular kinase which regulates anti‐apoptotic pathways on the other, in this study we investigated whether HA affects Akt phosphorylation prior to and following injury and whether this step is required for development of HA‐induced neuroprotection. Akt phosphorylation was blocked using Triciribine (TCN), a compound shown to block the phosphorylation process without affecting upstream effectors of this kinase, and several post‐injury functional end‐point measures were subsequently evaluated. Acclimation led to a post‐injury increase in the levels of phosphorylated Akt, resulting in higher levels when compared with normothermic controls at 4 h post‐injury (63.6 ± 5.2% and 42.7 ± 3.7%, respectively, p ≤ 0.05). This increase was diminished following TCN administration. Post‐injury TCN treatment abolished the HA‐induced functional benefits, including effects on motor and cognitive functions as well as the attenuation of edema formation. We therefore suggest that Akt phosphorylation is essential for HA‐induced neuroprotection after traumatic brain injury.