Role of miR-146a in neural stem cell differentiation and neural lineage determination: relevance for neurodevelopmental disorders

ConclusionOur results demonstrate the dynamic roles ofmiR-146a in early neuronal development and provide new insight into the molecular events that linkmiR-146a overexpression to impaired neurodevelopment. This, in turn, may yield new therapeutic targets and strategies.
Source: Molecular Autism - Category: Molecular Biology Source Type: research

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AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/C...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionMEK-ERK and MNK-eIF4E pathways regulate protein translation, and our results suggest that aberrant translation distinct in TSC1/2-deficient NPCs could play a role in neurodevelopmental defects. Our data showing upregulation of these signaling pathways by rapamycin support a strategy to combine a MEK or a MNK inhibitor with rapamycin that may be superior for TSC-associated CNS defects. Importantly, our generation of isogenic sets of NPCs from TSC patients provides a valuable platform for translatome and large-scale drug screening studies. Overall, our studies further support the notion that early developmental eve...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
ConclusionsThis is the first report to show that humanNRXN1 α+/ − neurons derived from ASD patients ’ iPSCs present novel phenotypes of upregulated VGCCs and increased Ca2+ transients, which may facilitate the development of drug screening assays for the treatment of ASD.
Source: Molecular Autism - Category: Molecular Biology Source Type: research
We report here the derivation of familial iPSC lines from two controls and three ASD patients carrying NRXN1α+/−, using a non-integrating Sendai viral kit. The genotype and karyotype of the resulting iPSCs were validated by whole genome SNP array. All iPSC lines expressed comparable levels of pluripotency markers and could be differentiated into three germ layers.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT. Introduction Rett syndrome (RTT) is a progressive neurodevelopmental disorder. It primarily affects females, who show the first obvious symptoms within 6–18 months after birth. Among the characteristics are a regression of mental ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Authors: Pirozzi F, Nelson B, Mirzaa G Abstract Expansion of the human brain, and specifically the neocortex, is among the most remarkable evolutionary processes that correlates with cognitive, emotional, and social abilities. Cortical expansion is determined through a tightly orchestrated process of neural stem cell proliferation, migration, and ongoing organization, synaptogenesis, and apoptosis. Perturbations of each of these intricate steps can lead to abnormalities of brain size in humans, whether small (microcephaly) or large (megalencephaly). Abnormalities of brain growth can be clinically isolated or occur ...
Source: Dialogues in Clinical Neuroscience - Category: Neuroscience Tags: Dialogues Clin Neurosci Source Type: research
When Nichelle Obar learned she was pregnant with her second child last year, she never expected that her pregnancy, or her baby, would make history. But when the 40-year-old food-and-beverage coordinator from Hawaii and her fiancé Christopher Constantino went to their 18-week ultrasound, they learned something was wrong. The heart was larger than it should have been, and there was evidence that fluid was starting to build up around the organ as well. Both were signs that the fetus was working extra hard to pump blood to its fast-growing body and that its heart was starting to fail. Obar’s doctor knew what coul...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized medicine Source Type: news
Conclusions and ImplicationsThe results of this analysis suggest that while children diagnosed with CP and with access to stored CB differ from a broader population sample in terms of demographics, they have similar clinical severity and comorbidity profiles. As such, LUSTRE may serve as a valuable source of data for the characterization of individuals with CP, including individuals who have or will receive CB infusions.
Source: Research in Developmental Disabilities - Category: Disability Source Type: research
AbstractBackgroundIntegrating rare variation from trio family and case –control studies has successfully implicated specific genes contributing to risk of neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASD), intellectual disability (ID), developmental disorders (DDs), and epilepsy (EPI). For schizophrenia (SCZ), however, while sets of genes have been implicated through the study of rare variation, only two risk genes have been identified.MethodsWe used hierarchical Bayesian modeling of rare-variant genetic architecture to estimate mean effect sizes and risk-gene proportions, analyzing the la...
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
Conclusion: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O’Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice. Environ Health Perspect 125:82–88; http://dx.doi.org/10.1289/EHP211 *These authors contributed equally to this work. Address correspondence to F. Marchetti, Environmental Health Science and Research Bureau, Health Canada, 50 Colombine Driveway, Ot...
Source: EHP Research - Category: Environmental Health Authors: Tags: Research Articles January 2017 Source Type: research
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