| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Smoking cessation therapy with varenicline is associated with the increased risk of suicide or attempted suicide and depression, although varenicline exerts antidepressant-like effects as a partial agonist at α4β2 and full agonist at α7 nicotinic acetylcholine receptor (nAChR). These neuropsychiatric events may be attributed to the dysfunction of the neurovascular unit with hyperpermeability of the blood-brain barrier (BBB). The aim of this study is to determine nAChR subtype as a target for varenicline-indcued BBB hyperpermeability. We found that (1) brain endothelial barrier was impaired by a long term exposure of the α7 nAChR agonist, (2) brain pericytes were the highest responsive cell type to the α7 nAChR stimulation in releasing the matrix metalloproteinase-9, and (3) brain pericytes enhanced the α7 nAChR agonist-induced brain endothelial hyperpermeability. These findings suggest that varenicline would induce BBB dysfunction by stimulating α7 nAChR.
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