Schwann cells genetically engineered to express PSA show enhanced migratory potential without impairment of their myelinating ability in vitro

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Increased anxiety-related behavior, impaired cognitive function and cellular alterations in the brain of cend1-deficient mice

Cend1 is a neuronal-lineage specific modulator involved in coordination of cell cycle exit and differentiation of neuronal precursors. We have previously shown that Cend1−/− mice show altered cerebellar layering caused by increased proliferation of granule cell precursors, delayed radial granule cell migration and compromised Purkinje cell differentiation, leading to ataxic gait and deficits in motor coordination. To further characterize the effects of Cend1 genetic ablation we determined herein a range of behaviors, including anxiety and exploratory behavior in the elevated plus maze (EPM), associative learning in fear conditioning, and spatial learning and memory in the Morris water maze (MWM). We observed significant deficits in all tests, suggesting structural and/or functional alterations in brain regions such as the cortex, amygdala and the hippocampus. In agreement with these findings, immunohistochemistry revealed reduced numbers of γ amino butyric acid (GABA) GABAergic interneurons, but not of glutamatergic projection neurons, in the adult cerebral cortex. Reduced GABAergic interneurons were also observed in the amygdala, most notably in the basolateral nucleus. The paucity in GABAergic interneurons in adult Cend1−/− mice correlated with increased proliferation and apoptosis as well as reduced migration of neuronal progenitors from the embryonic medial ganglionic eminence (MGE), the origin of these cells. Further we noted reduced GABAergic neurons and aberrant neurogenesis in the adult dentate gyrus (DG) of the hippocampus, which has been previously shown to confer spatial learning and memory deficits. Our data highlight the necessity of Cend1 expression in the formation of a structurally and functionally normal brain phenotype. © 2019 Segklia, Stamatakis, Stylianopoulou, Lavdas and Matsas

Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons

Strategies to enhance neural stem/precursor cell (NPC) capacity to yield multipotential, proliferative, and migrating pools of cells that can efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. Here, we have generated a lentiviral vector for expression of insulin-like growth factor-I (IGF-1) and investigated the impact of IGF-1 transduction on the properties of cultured NPCs (IGF-1-NPCs). Under proliferative conditions, IGF-1 transduction promoted cell cycle progression via cyclin D1 up-regulation and Akt phosphorylation. Remarkably upon differentiation-inducing conditions, IGF-1-NPCs cease to proliferate and differentiate to a greater extent into neurons with significantly longer neurites, at the expense of astrocytes. Moreover, using live imaging we provide evidence that IGF-1 transduction enhances the motility and tissue penetration of grafted NPCs in cultured cortical slices. These results illustrate the important consequence of IGF-1 transduction in regulating NPC functions and offer a potential strategy to enhance the prospective repair potential of NPCs. © 2010 International Society for Neurochemistry

Deleted in Azoospermia-Like (DAZL) gene-expressing cells in human amniotic fluid: a new source for germ cells research?

Objective: To evaluate whether amniotic fluid cells contain a germ-like cell subpopulation. Design: Experimental study. Setting: University hospital. Patient(s): None. Intervention(s): Cells from human amniotic fluid samples were analyzed for messenger RNA expression of Deleted in Azoospermia-Like gene (DAZL) and Oct-4 by reverse transcriptase polymerase chain reaction. DAZL and C-kit protein expression was assessed by flow cytometry. Immunocytochemistry also was performed to determine DAZL-, stage-specific embryonic antigen 4 (SSEA-4)-, and Oct-4-positive cells. Main Outcome Measure(s): DAZL gene expression in amniotic fluid cells. Result(s): Reverse transcriptase polymerase chain reaction, flow cytometric, and immunocytochemical analyses revealed that human amniotic fluid consists of a distinct cell population that expresses DAZL, C-kit, SSEA-4, and Oct-4. Conclusion(s): Our results suggest that human amniotic fluid represents a new source for the isolation of human DAZL-, C-kit-, SSEA-4-, and Oct-4-positive stem cells without raising the ethical issues associated with human embryonic research. © 2008 American Society for Reproductive Medicine

Long-term intradialytic hybrid exercise training on fatigue symptoms in patients receiving hemodialysis therapy

Purpose: Hemodialysis (HD) patients suffer from generalized weakness, exercise intolerance and muscle atrophy, all leading to generalized fatigue and lack of energy. HD patients spend at least 50% of their time in a functionally “switch off” mode with their fatigue sensations reaching a peak in the immediate hours after the dialysis session. The purpose of the current study was to assess the effectiveness of a nine-month hybrid intradialytic exercise program on fatigue symptoms occurring during and after hemodialysis session. Methods: Twenty stable hemodialysis patients were included in the study (59 ± 13.7 years; 16 males). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training during HD. Aspects related to physical and generalized fatigue were assessed via validated questionnaires, while physical performance was assessed by a battery of tests, before and after the intervention period. Results: Exercise capacity and physical performance were increased by an average of 65 and 40%, respectively. Patients reported feeling better during post-dialysis hours in question 1 (p = 0.000), question 3 (p = 0.009) and question 4 (p = 0.003) after the 9-month intervention. In addition, exercise training improved scores in cognitive function (p = 0.037), vitality (p = 0.05), depression (p = 0.000) and fatigue (p = 0.039). Conclusion: The present study showed that a 9-month hybrid (aerobic + resistance) exercise training program improved symptoms of post-dialysis fatigue and overall general perception of fatigue. Hybrid exercise training is a safe and effective non-pharmacological approach to ameliorate fatigue symptoms in HD patients. Trial registration number: Trial registration number The study is registered at ClinicalTrials.gov (NCT01721551, 2012) as a clinical trial. © 2021, Springer Nature B.V

The effect of cold dialysis in motor and sensory symptoms of RLS/WED occurring during hemodialysis: A double-blind study

Restless legs syndrome/Willis–Ekbom disease (RLS/WED) is a common sensorimotory disorder affecting almost 30% of hemodialysis (HD) patients. RLS/WED induces discomfort during rest hours, and its symptoms have also been observed during HD sessions. Anecdotal reports suggest that cooling the dialysate solution during dialysis could help patients overcome those symptoms and improve restlessness. The aim of this double-blind study was to assess whether a reduction of the dialysate temperature by 1°C could reduce motor and sensory symptoms of RLS/WED occurring during HD. Thirty-two HD patients participated in the study. Patients were divided into two groups: the RLS (N=16) and the non-RLS groups (N=16). Patients were studied on two different scenarios for two consecutive HD sessions, 1 week apart: 1) standard temperature of the dialysate (37°C) and 2) low temperature of the dialysate (36°C cold dialysis scenario). In all sessions, motor (leg movement per hour of HD [LM/hHD]) and sensory symptoms were assessed. The reduction of dialysate temperature by 1°C was effective in reducing motor symptoms as they assessed the LM/hHD by 36% only in patients with RLS, while a significant interaction was found between “LM/hHD affected by temperature” and “RLS status” (p = 0.039). Sensory symptoms also reduced by 10% after the reduction of the dialysate temperature. The reduction of the dialysate temperature by 1°C reduced motor symptoms by 36–54% and sensory symptoms by 10% in HD patients with RLS/WED. Cold dialysis could be considered a safe nonpharma-cological approach for the amelioration of RLS/WED symptoms occurring during HD. ASAIO Journal 2018; 64:110–114. Copyright © 2017 by the ASAIO

Erratum: SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila (Human Molecular Genetics (2017) 26:13 (2412-2425) DOI: 10.1093/hmg/ddx132)

The authors of the article "SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila" would like to report the incorrect description of an iPSC line in the paper. Authentication analysis at Coriell Institute for Medical Research (Camden, New Jersey) revealed that the cell line named iPS-HFF in the article was not derived from newborn foreskin fibroblasts (as reported in Table S2) but from cells of a female patient with osteogenesis imperfecta (GM17602/GM17604), carrier of a heterozygous missense mutation (p.G700C; NM_000089) in the COL1A2 gene. Repeated karyotype analysis performed for the line named iPS-HFF showed a normal female karyotype, which means that the male karyotype displayed in Figure S4B is mislabeled and was not derived from iPS-HFF. Differentiated dopaminergic neurons from the line named iPS-HFF were examined for mitochondrial complex I activity (Figure 4A) and mitochondrial morphology (Figure 4B) as one of in total three analyzed control iPSC lines compared to Parkin mutant lines. Importantly, both experiments display robust phenotypes and are replicative analysis of results shown in Parkin knockdown SH-SY5Y cells: Loss-of-Parkin leads to decreased complex I activity (Figure 2B) and an increased amount of fragmented mitochondria (Figure 2D), while overexpression of SLP-2 rescues both phenotypes. This confirms that the analyzed data in Figure 4 are not influenced by the COL1A2 mutation. Furthermore, mutations in the COL1A2 gene have not been associated with neurodegenerative diseases and the symptoms of neurological movement disorders have not been described for osteogenesis imperfecta. Therefore, the fact that this particular cell line is from a diseased individual with osteogenesis imperfecta rather than a healthy control does not alter the interpretation of our results as pertaining to rescue of mitochondrial phenotypes as described in the manuscript. The authors would like to apologize for this mistake