title: The role and dynamics of β-catenin in precondition induced neuroprotection after traumatic brain injury.
abstract: Preconditioning via heat acclimation (34°C 30 d) results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1α. In the present study we investigated the Akt downstream GSK3β/β-catenin pathway and focused on post injury alternations of β catenin and its impact on the cellular response in preconditioned heat acclimated mice. We found that the reduction in motor disability is accompanied with attenuation of depressive like behavior in heat acclimated mice that correlates with the GSK3β phosphorylation state. Concomitantly, a robust β catenin phosphorylation is not followed by its degradation, or by reduced nuclear accumulation. Enhanced tyrosine phosphorylation of β catenin in the injured area weakens the β catenin-N cadherin complex. Membrane β catenin is transiently reduced in heat acclimated mice and its recovery 7 days post TBI is accompanied by induction of the synaptic marker synaptophysin. We suggest a set of cellular events following traumatic brain injury in heat acclimated mice that causes β catenin to participate in cell-cell adhesion alternations rather than in Wnt signaling. These events may contribute to synaptogenesis and the improved motor and cognitive abilities seen heat acclimated mice after traumatic brain injury.
authors.affiliation: Department of Pharmacology, The Hebrew University, Jerusalem, Israel ; Laboratory of Environmental Physiology, The Hebrew University, Jerusalem, Israel.
authors.forename: Gali
authors.initials: G
authors.lastname: Umschweif
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Alexandrovich
authors.forename: Victoria
authors.initials: V
authors.lastname: Trembovler
authors.forename: Michal
authors.initials: M
authors.lastname: Horowitz
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3