Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits
ConclusionOur results show thatmiR-146a expression is critical for correct differentiation of neural stem cell during brain development and provide for the first time a strong argument for a postnatal role ofmiR-146a in regulating hippocampal-dependent memory. Furthermore, the demonstration that theMir146a−/− mouse recapitulates several aspects reported in DBD patients, including impaired neurogenesis, abnormal brain anatomy, and working and spatial memories deficits, provides convincing evidence that the dysregulation ofmiR146a contributes to the pathogenesis of DBDs.
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.
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.
Using neurons grown from stem cells, EU-funded researchers are revealing more about mutations that lead to autism, schizophrenia and intellectual disability which researchers hope will lead to new drug targets for personalised medicine.
Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder Deborah K. Sokol1, Bryan Maloney2, Cara J. Westmark3 and Debomoy K. Lahiri2,4* 1Pediatrics Section, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States2Indiana Alzheimers Disease Center, Department of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States3Department of Neurology, University of Wisconsin, Madison, WI, United States4Department of Medical and Molecular Genetics, Indiana Un...
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...
ConclusionsAlterations in F-actin polymerization and WRC have been found in a number of genetic subgroups of IDD and ASD. Thus, LS, a very rare genetic condition, is linked to a more expansive family of genes responsible for neurodevelopmental disorders that have shared pathogenic features.
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...
Conclusions: Together our findings indicate that, despite the down-regulation of NMD factors, functional NMD is critical for neuronal differentiation. We propose that the neurodevelopmental phenotype of UPF3B missense mutation is caused by impairment of NMD function altering neuronal differentiation.