title: Akt phosphorylation is required for heat acclimation-induced neuroprotection.
abstract: Long-term heat exposure, known as heat acclimation (HA; 30 days at 34 +/- 1 degrees 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.
authors.affiliation: Department of Pharmacology, The Hebrew University, Jerusalem, Israel.
authors.forename: Na'ama A
authors.initials: NA
authors.lastname: Shein
authors.forename: Jeanna
authors.initials: J
authors.lastname: Tsenter
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Alexandrovich
authors.forename: Michal
authors.initials: M
authors.lastname: Horowitz
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000064:Acclimatization / Q000502:physiology*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D006358:Hot Temperature / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D051057:Proto-Oncogene Proteins c-akt