Limits...
Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-β (Aβ) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with Aβ levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of Aβ decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Transplantation of human amniotic membrane-derived mesenchymal stem cells (AMMSCs) attenuates spatial learning and memory function in Alzheimer's disease (AD) transgenic mice. (A) Mice in each group were subjected to the water maze test every day and the escape latency was measured to examine the spatial learning ability of mice. AMMSC transplantation ameliorated spatial memory in the AD mice. A probe test without a platform was performed one day after the last training trial to investigate spatial memory. (B) Effect of AMMSC transplantation on escape latency during the memory trial. (C) Number of platform location crossings and (D) time spent in target quadrant during the spatial memory test in the probe trial. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4998013&req=5

f2-ol-0-0-4857: Transplantation of human amniotic membrane-derived mesenchymal stem cells (AMMSCs) attenuates spatial learning and memory function in Alzheimer's disease (AD) transgenic mice. (A) Mice in each group were subjected to the water maze test every day and the escape latency was measured to examine the spatial learning ability of mice. AMMSC transplantation ameliorated spatial memory in the AD mice. A probe test without a platform was performed one day after the last training trial to investigate spatial memory. (B) Effect of AMMSC transplantation on escape latency during the memory trial. (C) Number of platform location crossings and (D) time spent in target quadrant during the spatial memory test in the probe trial. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.

Mentions: To investigate the effect of hAMMSC transplantation on the learning and memory of AD transgenic mice, a Morris water maze test was conducted 3 weeks after hAMMSC transplantation. C57BL/6J-APP transgenic mice overexpress the APP695 gene and secrete endogenous Aβ, contributing to the deposition of Aβ mainly in the neurons of the cerebral cortex and hippocampus. During the acquisition training phase of the water maze test, the PBS-injected control group exhibited notable learning and memory dysfunction compared with the normal control mice, whereas the hAMMSCs-injected group located the hidden platform significantly faster than the PBS-injected control group, and demonstrated no significantly difference from the normal control group, indicating significantly improved learning and memory function (Fig. 2A). Then, we performed a probe test one day after the last training trial to examine the spatial memory. The platform was removed and the time taken to reach the same zone was recorded within 60 sec. The PBS-injected control group spent less time in the target quadrant than the hAMMSC group and the normal mice (P<0.01; Fig. 2B-D), demonstrating that the deficit in spatial memory was rescued by hAMMSC transplantation.


Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice
Transplantation of human amniotic membrane-derived mesenchymal stem cells (AMMSCs) attenuates spatial learning and memory function in Alzheimer's disease (AD) transgenic mice. (A) Mice in each group were subjected to the water maze test every day and the escape latency was measured to examine the spatial learning ability of mice. AMMSC transplantation ameliorated spatial memory in the AD mice. A probe test without a platform was performed one day after the last training trial to investigate spatial memory. (B) Effect of AMMSC transplantation on escape latency during the memory trial. (C) Number of platform location crossings and (D) time spent in target quadrant during the spatial memory test in the probe trial. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998013&req=5

f2-ol-0-0-4857: Transplantation of human amniotic membrane-derived mesenchymal stem cells (AMMSCs) attenuates spatial learning and memory function in Alzheimer's disease (AD) transgenic mice. (A) Mice in each group were subjected to the water maze test every day and the escape latency was measured to examine the spatial learning ability of mice. AMMSC transplantation ameliorated spatial memory in the AD mice. A probe test without a platform was performed one day after the last training trial to investigate spatial memory. (B) Effect of AMMSC transplantation on escape latency during the memory trial. (C) Number of platform location crossings and (D) time spent in target quadrant during the spatial memory test in the probe trial. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
Mentions: To investigate the effect of hAMMSC transplantation on the learning and memory of AD transgenic mice, a Morris water maze test was conducted 3 weeks after hAMMSC transplantation. C57BL/6J-APP transgenic mice overexpress the APP695 gene and secrete endogenous Aβ, contributing to the deposition of Aβ mainly in the neurons of the cerebral cortex and hippocampus. During the acquisition training phase of the water maze test, the PBS-injected control group exhibited notable learning and memory dysfunction compared with the normal control mice, whereas the hAMMSCs-injected group located the hidden platform significantly faster than the PBS-injected control group, and demonstrated no significantly difference from the normal control group, indicating significantly improved learning and memory function (Fig. 2A). Then, we performed a probe test one day after the last training trial to examine the spatial memory. The platform was removed and the time taken to reach the same zone was recorded within 60 sec. The PBS-injected control group spent less time in the target quadrant than the hAMMSC group and the normal mice (P<0.01; Fig. 2B-D), demonstrating that the deficit in spatial memory was rescued by hAMMSC transplantation.

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-&beta; (A&beta;) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with A&beta; levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of A&beta; decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus