A hexanucleotide repeat expansion (HRE), (GGGGCC)n, in C9orf72 is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here researchers identified a molecular mechanism by which structural polymorphism of the HRE leads to ALS/FTD pathology and defects. [Nature] Abstract | Press Release Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis
Researchers showed that selective nuclear factor-kappa B (NF-κB) inhibition in amyotrophic lateral sclerosis (ALS) astrocytes is not sufficient to rescue motor neuron (MN) death. However, the localization of NF-κB activity and subsequent deletion of NF-κB signaling in microglia rescued MNs from microglial-mediated death in vitro and extended survival in ALS mice by impairing proinflammatory microglial activation. [Neuron] Abstract
Dendrite Self-Avoidance Requires Cell-Autonomous Slit/Robo Signaling in Cerebellar Purkinje Cells
Scientists report a role for the secreted molecule Slit2 and its receptor Robo2 in self-avoidance of cerebellar Purkinje cells (PCs). Both molecules are highly expressed by PCs, and their deletion leads to excessive dendrite self-crossing without affecting arbor size and shape. [Neuron] Abstract
Identification of a Cellular Node for Motor Control Pathways
The authors identified a population of molecularly defined motor synergy encoder neurons in the mouse spinal cord that may represent a central node in neural pathways for voluntary and reflexive movement. [Nat Neurosci] Abstract
A Role for Bicaudal-D2 in Radial Cerebellar Granule Cell Migration
Bicaudal-D2 (BICD2)-deficient mice develop disrupted laminar organization of cerebral cortex and the cerebellum, pointing to impaired radial neuronal migration. Using astrocyte and granule cell specific inactivation of BICD2, investigators showed that the cerebellar migration defect is entirely dependent upon BICD2 expression in Bergmann glia cells. [Nat Commun] Abstract
Molecular Adaptations of Striatal Spiny Projection Neurons during Levodopa-Induced Dyskinesia
Researchers identified distinct cell-type-specific gene-expression changes that occur in subclasses of spiny projection neurons upon induction of a parkinsonian lesion followed by chronic levodopa treatment. [Proc Natl Acad Sci USA] Abstract
Genome-Wide shRNA Screen Revealed Integrated Mitogenic Signaling between Dopamine Receptor D2 (DRD2) and Epidermal Growth Factor Receptor (EGFR) in Glioblastoma
Treatment with independent si-/shRNAs against DRD2 or with DRD2 antagonists suppressed the growth of patient-derived glioblastoma lines both in vitro and in vivo. [Oncotarget] Abstract | Press Release
BDNF Pre-Treatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery after Transplantation in Hypoxic-Ischemic Stroke
Researchers evaluated if pre-treatment of neural stem cells with brain derived neurotrophic factor (BDNF) prior to transplantation improves cell engraftment and functional recovery following hypoxic-ischemia. [Cell Transplant] Abstract
Increased Precursor Cell Proliferation after Deep Brain Stimulation for Parkinson’s Disease: A Human Study
Deep brain stimulation (DBS) has been used for more than a decade to treat Parkinson’s disease; however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the “germinal niches,” researchers sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly. [PLoS One] Full Article
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation
Investigators showed that human induced pluripotent stem cell (iPSC)-derived dopaminergic (DA) progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. They induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. [Stem Cell Rep] Full Article | Graphical Abstract | Press Release