Molecular mechanisms of the restoration of human APP transgenic mouse cognitive dysfunction after transplant of human iPS cell-derived neural cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26501005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Arimitsu Nagisa 聖マリアンナ医科大学, 医学部, 助教 (40408688)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 再生医療

Outline of Final Research Achievements

We examined the molecular mechanisms involved in the alleviation of cognitive dysfunction in transplanted Alzheimer's disease model mice . Neural cells derived from hiPS cells were transplanted to the hilus of the dentate gyrus. After transplant, mice showed improvement in cognitive function. Human choline acetyltransferase (ChAT)-positive cholinergic neurons and small number of vesicular GABA transporter (VGAT)-positive neurons were distributed throughout the cortex of the grafted mice. Human and mouse ChAT and GABA-positive neurons and their receptors of both human origin and mouse origin were significantly increased in the cortex and hippocampus.
The receptor-positive neurons expressed phosphorylated Akt and c-fos in the cortex. And we also confirmed that paracrine factors such as Reelin expressed in the injected area. These suggest that the grafted and host neurons may form positive feedback loops via neurotransmitter secretion in both the cerebral cortex and hippocampus.

Free Research Field

分子生物学