| RRC ID |
37594
|
| 著者 |
Fujiwara N, Shimizu J, Takai K, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
|
| タイトル |
Cellular and molecular mechanisms of the restoration of human APP transgenic mouse cognitive dysfunction after transplant of human iPS cell-derived neural cells.
|
| ジャーナル |
Exp Neurol
|
| Abstract |
Cholinergic neuronal loss is a common finding in patients with Alzheimer's disease (AD) and AD model mice. We previously transplanted neurons derived from human induced pluripotent stem (iPS) cells into the hippocampus of human amyloid precursor protein transgenic AD model mice. In the present study, we examined the cellular and molecular mechanisms involved in the alleviation of cognitive dysfunction in transplanted mice. After transplant, mice showed improvement in cognitive function, confirming our previous findings. Human choline acetyltransferase (ChAT)-positive cholinergic neurons were distributed throughout the cortex of the grafted mice. Human and mouse ChAT-positive neurons and alpha7 nicotinic acetylcholine receptor (α7nAChR)-positive neurons were significantly increased in the cortex and hippocampus of the grafted mice compared with the vehicle-injected mice. In addition, human and mouse vesicular GABA transporter (VGAT)-positive neurons were located mainly in the hippocampus and, though the number was small, human VGAT-positive neurons were observed in the cortex. In the grafted mouse cortex, the number of GABA receptor (GABAR)-positive neurons of both human origin and mouse origin were significantly increased compared with those in the vehicle-injected mouse cortex. The α7nAChR-positive and GABAR-positive neurons expressed phosphorylated Akt and c-fos in the cortex, suggesting that these receptor-expressing neurons were possibly activated by the neurotransmitters secreted from the grafted neurons. Collectively, the grafted and host neurons may form positive feedback loops via neurotransmitter secretion in both the cerebral cortex and hippocampus, leading to alleviation of cognitive dysfunction in dementia model mice.
|
| 巻・号 |
271
|
| ページ |
423-31
|
| 公開日 |
2015-9-1
|
| DOI |
10.1016/j.expneurol.2015.07.008
|
| PII |
S0014-4886(15)30041-8
|
| PMID |
26196079
|
| MeSH |
Amyloid beta-Protein Precursor / genetics*
Animals
Choline O-Acetyltransferase / metabolism
Cognition Disorders / genetics*
Cognition Disorders / surgery*
Disease Models, Animal
Gene Expression Regulation / physiology
Humans
Induced Pluripotent Stem Cells / physiology*
Maze Learning
Mice
Mice, Transgenic
Nerve Tissue Proteins / metabolism
Neurons / metabolism
Neurons / physiology*
Oncogene Protein v-akt / metabolism
Receptors, GABA / metabolism
Recovery of Function / physiology*
Stem Cell Transplantation*
Time Factors
Vesicular Inhibitory Amino Acid Transport Proteins / metabolism
alpha7 Nicotinic Acetylcholine Receptor / metabolism
|
| IF |
4.691
|
| 引用数 |
9
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| ヒト・動物細胞 |
201B7(HPS0063)
253G1(HPS0002) |
