scholarly journals Human Neural Stem Cells Encoding ChAT Gene Restore Cognitive Function via Acetylcholine Synthesis, Aβ Elimination, and Neuroregeneration in APPswe/PS1dE9 Mice

2020 ◽  
Vol 21 (11) ◽  
pp. 3958
Author(s):  
Dongsun Park ◽  
Ehn-Kyoung Choi ◽  
Tai-Hyoung Cho ◽  
Seong Soo Joo ◽  
Yun-Bae Kim
Keyword(s):  
Stem Cell ◽  
Cognitive Function ◽  
Memory Function ◽  
Memory Deficits ◽  
Therapeutic Approaches ◽  
Human Neural Stem Cells ◽  
Ache Inhibitors ◽  
Human Neural Stem Cell ◽  
Memory Acquisition ◽  
Ad Therapy

In Alzheimer disease (AD) patients, degeneration of the cholinergic system utilizing acetylcholine for memory acquisition is observed. Since AD therapy using acetylcholinesterase (AChE) inhibitors are only palliative for memory deficits without slowing or reversing disease progress, there is a need for effective therapies, and stem cell-based therapeutic approaches targeting AD should fulfill this requirement. We established a human neural stem cell (NSC) line encoding choline acetyltransferase (ChAT) gene, an acetylcholine-synthesizing enzyme. APPswe/PS1dE9 AD model mice transplanted with the F3.ChAT NSCs exhibited improved cognitive function and physical activity. Transplanted F3.ChAT NSCs in the AD mice differentiated into neurons and astrocytes, produced ChAT protein, increased the ACh level, and improved the learning and memory function. F3.ChAT cell transplantation reduced Aβ deposits by recovering microglial function; i.e., the down-regulation of β-secretase and inflammatory cytokines and up-regulation of Aβ-degrading enzyme neprilysin. F3.ChAT cells restored growth factors (GFs) and neurotrophic factors (NFs), and they induced the proliferation of NSCs in the host brain. These findings indicate that NSCs overexpressing ChAT can ameliorate complex cognitive and physical deficits of AD animals by releasing ACh, reducing Aβ deposit, and promoting neuroregeneration by the production of GFs/NFs. It is suggested that NSCs overexpressing ChAT could be a candidate for cell therapy in advanced AD therapy.

scholarly journals Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2)

2020 ◽  
Vol 91 (4) ◽  
pp. 396-401 ◽  
Author(s):  
Keith W Muir ◽  
Diederik Bulters ◽  
Mark Willmot ◽  
Nikola Sprigg ◽  
Anand Dixit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Multicentre Study ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Upper Limb ◽  
Limb Movement ◽  
Human Neural Stem Cells ◽  
Human Neural Stem Cell ◽  
Cell Implantation

BackgroundHuman neural stem cell implantation may offer improved recovery from stroke. We investigated the feasibility of intracerebral implantation of the allogeneic human neural stem cell line CTX0E03 in the subacute—chronic recovery phase of stroke and potential measures of therapeutic response in a multicentre study.MethodsWe undertook a prospective, multicentre, single-arm, open-label study in adults aged >40 years with significant upper limb motor deficits 2–13 months after ischaemic stroke. 20 million cells were implanted by stereotaxic injection to the putamen ipsilateral to the cerebral infarct. The primary outcome was improvement by 2 or more points on the Action Research Arm Test (ARAT) subtest 2 at 3 months after implantation.FindingsTwenty-three patients underwent cell implantation at eight UK hospitals a median of 7 months after stroke. One of 23 participants improved by the prespecified ARAT subtest level at 3 months, and three participants at 6 and 12 months. Improvement in ARAT was seen only in those with residual upper limb movement at baseline. Transient procedural adverse effects were seen, but no cell-related adverse events occurred up to 12 months of follow-up. Two deaths were unrelated to trial procedures.InterpretationAdministration of human neural stem cells by intracerebral implantation is feasible in a multicentre study. Improvements in upper limb function occurred at 3, 6 and 12 months, but not in those with absent upper limb movement at baseline, suggesting a possible target population for future controlled trials.FundingReNeuron, Innovate UK (application no 32074-222145).Trial registration numberEudraCT Number: 2012-003482-18

Quantification of Human Neural Stem Cell Fate Using Volocity® 3D Image Analysis Software

2012 ◽  
Vol 20 (5) ◽  
pp. 34-36
Author(s):  
Katja Piltti ◽  
Martin Daffertshofer ◽  
Brian Cummings
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Brain Injuries ◽  
Cell Types ◽  
Neural Function ◽  
Analysis Software ◽  
Stem Cell Fate ◽  
Human Neural Stem Cells ◽  
Human Neural Stem Cell ◽  
Strong Focus

The promise of stem cell therapy offers hope for the treatment of many human diseases and injuries. Spinal cord and traumatic brain injuries can cause the loss of neurons and glial cells. These lost cells may be partially replaced by transplanting multipotent human neural stem cells (hNSCs), which can differentiate into specialized neural cell types. The potential for these remarkable cells to promote recovery of neural function has made them a strong focus of researchers in this field.

scholarly journals Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model

2020 ◽  
Vol 21 (14) ◽  
pp. 4901
Author(s):  
Minsook Ye ◽  
Bong Hee Han ◽  
Jin Su Kim ◽  
Kyungsoo Kim ◽  
Insop Shim
Keyword(s):  
Cognitive Function ◽  
Glucose Uptake ◽  
Rat Brain ◽  
Morris Water Maze ◽  
Rat Model ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Memory Deficits ◽  
Avoidance Task

Background: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. Methods: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg−1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. Results: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. Conclusion: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer’s disease.

scholarly journals Efficacy of Different Types of Exercise on Cognitive Function in People With MCI or Dementia: A Network Meta-Analysis

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 293-293
Author(s):  
Qiaoqin Wan ◽  
Xiuxiu Huang ◽  
Xiaoyan Zhao ◽  
Bei Li ◽  
Ying Cai ◽  
...  
Keyword(s):  
Executive Function ◽  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Meta Analysis ◽  
Memory Function ◽  
Controlled Trials ◽  
Exercise Interventions ◽  
Exercise Treatment ◽  
Different Types ◽  
Global Cognition

Abstract With the accelerating progress of population aging, cognitive dysfunction is becoming increasingly prevalent. Exercise, as a promising non-pharmaceutical therapy, showed favorable effects on cognitive function. But which type is the most effective exercise treatment is still unclear. This study compared the efficacy of different types of exercise interventions based on network meta-analysis and aimed to explore the optimal exercise treatment for cognitive decline. The electronic databases of PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, SPORTDiscus, PsycInfoy, and OpenGrey were searched from inception to September 2019. We only included randomized controlled trials that examined the effectiveness of exercise interventions in people with MCI or dementia. Primary outcomes were global cognition, executive function and memory function. Standard mean difference (SMD) and its 95% confidence interval (CI) were calculated to estimate the effect sizes. Finally, 73 articles with 5748 participants were included. The results showed all kinds of exercise interventions were effective on global cognition and resistance exercise was probably the most effective exercise treatment to prevent the decrease of global cognition (SMD=1.05, 95%CI 0.56-1.54), executive function (SMD=0.85, 95%CI 0.21-1.49) and memory function (SMD=0.32, 95%CI 0.01-0.63) for people with cognitive dysfunction. Subgroup analysis revealed multi-component exercise showed more favorable effects on global cognition (SMD=0.99, 95%CI 0.44-1.54) and executive function (SMD=0.72, 95%CI 0.06-1.38) in people with MCI. In conclusion, resistance exercise tended to be the optimal exercise type for people with cognitive dysfunction, especially for people with dementia. And multi-component exercise also should be recommended for people with MCI.

Abstract P783: Alpha 7 -Acetylcholine Receptor Signaling Reduces Neuronal Apoptosis After Subarachnoid Hemorrhage

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ari Dienel ◽  
Remya A Veettil ◽  
Kanako Matsumura ◽  
Peeyush Kumar T. ◽  
Spiros Blackburn ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Acetylcholine Receptor ◽  
Neuronal Apoptosis ◽  
Neuronal Survival ◽  
Memory Function ◽  
Memory Deficits ◽  
Long Term Memory ◽  
Term Memory ◽  
Receptor Knockout Mouse

Subarachnoid hemorrhage induces neuronal apoptosis which causes acute and long-term memory deficits. Ourhypothesis is that agonism of α7-acetylcholine receptors attenuates neuronal apoptosis and improves memorydeficits in SAH mice. Mice were randomly assigned into the experimental groups. One cohort was euthanizedone day after SAH to assess neuronal apoptosis and signaling pathways. A second cohort survived for 30 dayspost-SAH to test long-term memory function. Inhibitors and an α7-acetylcholine receptor knockout mouse wereused. Neurobehavioral performance was assessed on days 1-3, 5, 7, and 23-28. All outcomes were performedand all data was analyzed by a blinded investigator. The α7-acetylcholine receptor agonist prevented neuronalapoptosis and improved acute memory deficits caused by SAH via activation of the PI3K/Akt pathway in neurons.Agonism of the α7-acetylcholine receptor was beneficial in both male and female mice, although the protectionin females was significantly better than in male mice. α7-acetylcholine receptor agonism did not provide anybenefit in α7-acetylcholine receptor knockout mice subjected to SAH. Treatment with the α7-acetylcholinereceptor agonist for 3 days after SAH led to improved working memory one month after SAH suggesting thatacutely improving neuronal survival can have long-lasting benefits. The α7-acetylcholine receptor may be atherapeutic target for SAH which can promote neuronal survival acutely after SAH, but also confer long-lastingmemory benefits. The findings of this study support the α7-acetylcholine receptor as a treatment target whichmay attenuate the long-term memory deficits which SAH patients suffer from.

A multi-stem cell basis for craniosynostosis and calvarial mineralization

2021 ◽  
Author(s):  
Matthew Greenblatt ◽  
Seoyeon Bok ◽  
Alisha Yallowitz ◽  
Jason McCormick ◽  
Michelle Cung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Endochondral Ossification ◽  
Distinct Form ◽  
Therapeutic Approaches ◽  
Genetic Ablation ◽  
Cell Lineages ◽  
Specific Fraction ◽  
Maladaptive Response ◽  
Suture Fusion ◽  
Stem Cell Populations

Abstract Craniosynostosis is a group of disorders of premature calvarial sutural fusion. An incomplete understanding of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts has limited the development of non-surgical therapeutic approaches for craniosynostosis. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a recently reported CathepsinK (CTSK) lineage CSC (CTSK+ CSC)1 and a separate Discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2+ CSC) identified in this study. Deletion of Twist1, a gene associated with human craniosynostosis2,3, solely in CTSK+ CSCs is sufficient to drive craniosynostosis, however the sites destined to fuse surprisingly display a marked depletion of CTSK+ CSCs and a corresponding expansion of DDR2+ CSCs. This DDR2+ CSC expansion is a direct maladaptive response to CTSK+ CSC depletion, as partial suture fusion occurred after genetic ablation of CTSK+ CSCs. This DDR2+ CSC is a specific fraction of DDR2+ lineage cells that displayed full stemness features, establishing the presence of two distinct stem cell lineages in the sutures, with each population contributing to physiologic calvarial mineralization. DDR2+ CSCs mediate a distinct form of endochondral ossification where an initial cartilage template is formed but the recruitment of hematopoietic marrow is absent. Direct implantation of DDR2+ CSCs into suture sites was sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK+ CSCs. Lastly, the human counterparts of DDR2+ CSCs and CTSK+ CSCs are present in calvarial surgical specimens and display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface to modulate calvarial mineralization and suture patency.

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