Cerebrovascular unit disruption in bipolar disorder model: Involvement of redox signaling mechanism

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18865
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Kurauchi Yuki 熊本大学, 大学院生命科学研究部(薬), 助教 (70631638)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Na+, K+-ATPase / 脳血管障害 / 双極性障害 / 精神疾患

Outline of Final Research Achievements

In this study, I established novel in vitro model to evaluate the degeneration mechanism of cerebrovascular unit. I prepared brain slices containing prefrontal cortex region from neonatal rats, and treated ouabain, an inhibitor of Na+, K+-ATPase. Treatment with ouabain induced degeneration of cerebrovascular endothelial cells, but not pericytes. For the protective mechanism of cerebrovascular endothelial cells and pericytes, I found that activation of PI-3kinase/Akt signaling pathway plays an endogenous protective mechanism against Na+, K+-ATPase dysfunction. Furthermore, I found that treatment with ouabain induces neuronal cell death and activates glial cells. These results suggest that activation of microglia and astrocytes causes degeneration of cerebrovascular endothelial cells and neurons in the prefrontal cortex region. These abnormalities may contribute to the pathophysiology of several psychiatric disorders including bipolar disorder.

Free Research Field

薬理学