No proinflammatory signature in CD34+ hematopoietic progenitor cells in multiple sclerosis patients.

Autologous hematopoietic stem cell transplantation (aHSCT) has been used as a therapeutic approach in multiple sclerosis (MS). However, it is still unclear if the immune system that emerges from autologous CD34+ hematopoietic progenitor cells (HPC) of MS patients is pre-conditioned to re-develop the proinflammatory phenotype. The objective of this article is to compare the whole genome gene and microRNA expression signature in CD34+ HPC of MS patients and healthy donors (HD). CD34+ HPC were isolated from peripheral blood of eight MS patients and five HD and analyzed by whole genome gene expression and microRNA expression microarray. Among the differentially expressed genes (DEGs) only TNNT1 reached statistical significance (logFC=3.1, p<0.01). The microRNA expression was not significantly different between MS patients and HD. We did not find significant alterations of gene expression or microRNA profiles in CD34+ HPCs of MS patients. Our results support the use of aHSCT for treatment of MS.

Pluripotent embryonic stem cells and multipotent adult germline stem cells reveal similar transcriptomes including pluripotency-related genes.

DNA microarray analysis was performed with mouse multipotent adult germline stem cells (maGSCs) and embryonic stem cells (ESCs) from different genetic backgrounds cultured under standard ESC-culture conditions and under differentiation-promoting conditions by the withdrawal of the leukemia inhibitory factor (LIF) and treatment with retinoic acid (RA). The analyzed undifferentiated cell lines are very similar based on their global gene expression pattern and show 97-99% identity dependent on the analyzed background. Only 621 genes are differentially expressed in cells derived from mouse 129SV-background and 72 genes show differences in expression in cells generated from transgenic Stra8-EGFP/Rosa26-LacZ-background. Both maGSCs and ESCs express the same genes involved in the regulation of pluripotency and even show no differences in the expression level of these genes. When comparing maGSCs with previously published signature genes of other pluripotent cell lines, we found that maGSCs shared a very similar gene expression pattern with embryonic germ cells (EGCs). Also after differentiation of maGSCs and ESCs the transcriptomes of the cell lines are nearly identical which suggests that both cell types differentiate spontaneously in a very similar way. This is the first study, at transcriptome level, to compare ESCs and a pluripotent cell line derived from an adult organism (maGSCs).

Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model.

The evidence for a protective role of physical activity on the risk and progression of Alzheimer's disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aß4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.

Social defeat leads to changes in the endocannabinoid system: An overexpression of calreticulin and motor impairment in mice.

Prolonged and sustained stimulation of the hypothalamo-pituitary-adrenal axis have adverse effects on numerous brain regions, including the cerebellum. Motor coordination and motor learning are essential for animal and require the regulation of cerebellar neurons. The G-protein-coupled cannabinoid CB1 receptor coordinates synaptic transmission throughout the CNS and is of highest abundance in the cerebellum. Accordingly, the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired as indicated the righting reflex and the rota-rod. The amount of the endocannabinoid 2-AG increased while CB1 mRNA and protein expression were downregulated after chronic stress. Transcriptome analysis revealed 319 genes differentially expressed by chronic psychosocial stress in the cerebellum; mainly involved in synaptic transmission, transmission of nerve impulse, and cell-cell signaling. Calreticulin was validated as a stress candidate gene. The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.