Potential for Stem Cells Therapy in Alzheimer’s Disease: Do Neurotrophic Factors Play Critical Role?

Alzheimer’s disease (AD) is one of the most common causes of dementia. Despite several decades of research in AD, there is no standard disease- modifying therapy available and currentlyapproved drugs provide only symptomatic relief. Stem cells hold immense potential to regenerate damaged tissues and are currently tested in some brain-related disorders, such as AD, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). We review stem cell transplantation studies using preclinical and clinical tools. We describe different sources of stem cells used in various animal models and explaining the putative molecular mechanisms that can rescue neurodegenerative disorders. The clinical studies suggest safety, efficacy and translational potential of stem cell therapy. The therapeutic outcome of stem cell transplantation has been promising in many studies, but no unifying hypothesis can convincingly explain the underlying mechanism. Some studies have reported paracrine effects exerted by these stem cells via the release of neurotrophic factors, while other studies describe the immunomodulatory effects exerted by the transplanted cells. There are also reports which indicate that stem cell transplantation might result in endogenous cell proliferation or replacement of diseased cells. In animal models of AD, stem cell transplantation is also believed to increase expression of synaptic proteins

CD34 and CD117 Stemness of Lineage-Negative Cells Reverses Memory Loss Induced by Amyloid Beta in Mouse Model

A majority of the neurodegenerative disorders including Alzheimer's disease are untreatable and occur primarily due to aging and rapidly changing lifestyles. The rodent Alzheimer's disease models are critical for investigating the underlying disease pathology and screening of novel therapeutic targets in preclinical settings. We aimed to characterize the stemness properties of human umbilical cord blood (hUCB) derived lineage-negative (Lin−) stem cells based on CD34 and CD117 expression as well as surface morphology using flow cytometry and scanning electron microscopy, respectively. The efficacy of the stem cells was tested by its capacity to rescue the injury caused by intrahippocampal delivery of varying doses of amyloid beta. The hUCB Lin− stem cells reversed memory loss due to Aβ42-induced injury more effectively at micromolar concentration, and not picomolar concentration. More studies are required to delineate the underlying molecular events associated with hUCB Lin− stem cells

The stem cell in the umbilical cord blood is not related to volume and nucleated cell count

547-549The percent CD 34⁺ cells in umbilical cord tremendously var-ied from sample to sample. Study conducted on 100 cryopre-served samples for their volume, nucleated cell count and CD 34⁺ cell count showed no correlation between the three. Correlation study between volume and nucleated cell count showed poor cor-relation, where as correlation between volume and CD 34⁺, nucle-ated cell count and CD 34⁺ cell count showed no/negative correla-tion. Graphical representation of volume vs. nucleated cell count, volume vs. CD 34⁺ cell count, and nucleated cell count vs. CD 34⁺ cell count show the same results. These results have important bearing in umbilical cord blood banking, since sample accep-tance/rejection at present is based only on volume of cord blood collected, which instead should be based on the number of CD 34⁺ stem cells

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down’s syndrome, Rett syndrome, and later onset of neuropsychological deficits. This review comprehensively describes the recent findings in the epigenetic landscape contributing to altered molecular profiles resulting in NDs. Furthermore, we will discuss potential avenues for future research to identify diagnostic markers and therapeutic epi-drugs to reverse these abnormalities in the brain as epigenetic marks are plastic and reversible in nature

Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring

10.3390/genes8060150GENES8

Pharmacological antagonism of EP2 receptor does not modify basal cardiovascular and respiratory function, blood cell counts, and bone morphology in animal models.

The EP2 receptor has emerged as a therapeutic target with exacerbating role in disease pathology for a variety of peripheral and central nervous system disorders. We and others have recently demonstrated beneficial effects of EP2 antagonists in preclinical models of neuroinflammation and peripheral inflammation. However, it was earlier reported that mice with global EP2 knockout (KO) display adverse phenotypes on fertility and blood pressure. Other studies indicated that EP2 activation with an agonist has a beneficial effect of healing fractured bone in animal models. These results impeded the development of EP2 antagonists, and EP2 antagonism as therapeutic strategy. To determine whether treatment with EP2 antagonist mimics the adverse phenotypes of the EP2 global KO mouse, we tested two EP2 antagonists TG11-77. HCl and TG6-10-1 in mice and rats while they are on normal or high-salt diet, and by two different administration protocols (acute and chronic). There were no adverse effects of the antagonists on systolic and diastolic blood pressure, heart rate, respiratory function in mice and rats regardless of rodents being on a regular or high salt diet. Furthermore, chronic exposure to TG11-77. HCl produced no adverse effects on blood cell counts, bone-volume and bone-mineral density in mice. Our findings argue against adverse effects on cardiovascular and respiratory systems, blood counts and bone structure in healthy rodents from the use of small molecule reversible antagonists for EP2, in contrast to the genetic ablation model. This study paves the way for advancing therapeutic applications of EP2 antagonists against diseases involving EP2 dysfunction

High glucose alters the DNA methylation of genes involved in axon guidance mechanism in human neural progenitor cells

5th International Anatomical Sciences and Cell Biology Conference (IASCBC)Malaysi