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ISDN2014_0331: The impact of comorbidity on event‐related brain topography in patients presenting chronic tic disorders and tourette syndrome
Author(s) -
Germain M.,
Chuang M.N.,
Sauvé G.,
O'Connor K.P.,
Blanchet P.J.,
Lavoie M.E.
Publication year - 2015
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2015.04.278
Subject(s) - mental health , center (category theory) , china , gerontology , psychology , humanities , sociology , medicine , art , psychiatry , history , chemistry , archaeology , crystallography
Instruction: TOPK (T-LAK-cell-originated protein kinase), a MAPKK-like serine/threonine kinase, is crucial for neural progenitor cells self-renewal, however, its function and molecular mechanism for cerebral ischemia reperfusion injury remains unknown. In this study, we demonstrated that phosphorylation of TOPK was increased in rat cortex following transient middle cerebral artery occlusion (tMCAO), and was colocalized with NeuN. Methods and results: To clarify its function, TOPK was overexpressed in PC12 neuronal cells, western blot displays elevated levels of antioxidative proteins peroxiredoxin 1 (Prx-1), Prx-2, heme oxygenase 1 (HO-1) and MnSOD, along with the activity of total SOD, which is in line with inhibition of peroxidation product MDA and 3-Nitrotyrosine upon H2O2 stimulation. As well, TOPK overexpression increased cell viability and reduced expression of Caspase-3 and Caspase-12 in PC12 cells upon H2O2 exposure. Furthermore, p-ERK level was increased by TOPK overexpression, and antioxidative protection afforded by TOPK was abolished by blocking ERK pathway in PC12 cells. In vivo, intracerebroventricular injection of TOPK overexpression vector reduced the infarct volume and neuronal apoptosis after tMCAO, increased total SOD activity and decreased ROS production in the cortex. Conclusion: Collectively, these data reveal that activating TOPK confers neuroprotection against focal cerebral ischemia reperfusion injury by its antioxidative effect partly through activating ERK pathway.