Details

Autor(en) / Beteiligte

• Maurin, Hervé
• Lechat, Benoit
• Borghgraef, Peter
• Devijver, Herman
• Jaworski, Tomasz
• Van Leuven, Fred

Titel

Terminal hypothermic T au. P 301 L mice have increased Tau phosphorylation independently of glycogen synthase kinase 3α/β

Ist Teil von

• The European journal of neuroscience, 2014-07, Vol.40 (2), p.2442-2453

Erscheinungsjahr

2014

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• Abstract The microtubule‐associated protein Tau is responsible for a large group of neurodegenerative disorders, known as tauopathies, including Alzheimer's disease. Tauopathy result from augmented and/or aberrant phosphorylation of Tau. Besides aging and various genetic and epigenetic defects that remain largely unknown, an important non‐genetic agent that contributes is hypothermia, eventually caused by anesthesia. Remarkably, tauopathy in brains of hibernating mammals is not pathogenic, and, because it is fully reversible, is even considered to be neuroprotective. Here, we assessed the terminal phase of Tau.P301L mice and bigenic crosses with mice lacking glycogen synthase kinase 3 ( GSK 3)α completely, or GSK 3β specifically in neurons. We also analysed bi GT bigenic mice that co‐express Tau.P301L with GSK 3β.S9A and develop severe forebrain tauopathy with age. We found that the precocious mortality of Tau.P301L mice was typified by hypothermia that aggravated Tau phosphorylation, but, surprisingly, independently of GSK 3α/β. The important contribution of hypothermia at the time of death of mice with tauopathy suggests that body temperature should be included as a parameter in the analysis of pre‐clinical models, and, by extension, in patients suffering from tauopathy.