Viscoelasticity and Volume of Cortical Neurons under Glutamate Excitotoxicity and Osmotic Challenges

Scientists studied the effects of glutamate-induced excitotoxicity, external osmotic pressure, and inhibition of actin polymerization on the viscoelastic properties and volume of neurons.
[Biophysical Journal]
Efremov, Y. M., Grebenik, E. A., Sharipov, R. R., Krasilnikova, I. A., Kotova, S. L., Akovantseva, A. A., Bakaeva, Z. V., Pinelis, V. G., Surin, A. M., & Timashev, P. S. (2020). Viscoelasticity and Volume of Cortical Neurons under Glutamate Excitotoxicity and Osmotic Challenges. Biophysical Journal, 0(0). https://doi.org/10.1016/j.bpj.2020.09.022 Cite
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Aclipse Therapeutics Awarded AUD 1 Million Grant from FightMND

Aclipse Therapeutics Inc. was awarded an AUD 1 million drug development research grant from FightMND, the largest independent funder of amyotrophic lateral sclerosis (ALS) research in Australia. The grant supported the translational development of M102, a drug candidate for the treatment of ALS, also known as motor neuron disease or Lou Gehrig’s disease. M102 showed promise to stop and reverse ALS disease progression, as evidenced by data in preclinical models.
[Aclipse Therapeutics Inc (BusinessWire LLC)]
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Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons

Investigators showed proof of concept of human glial progenitor cells (hGPCs) conversion using fetal cells and also established a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro.
[Stem Cell Reports]
Nolbrant, S., Giacomoni, J., Hoban, D. B., Bruzelius, A., Birtele, M., Chandler-Militello, D., Pereira, M., Ottosson, D. R., Goldman, S. A., & Parmar, M. (2020). Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.013 Cite
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CLR01 Protects Dopaminergic Neurons In Vitro and in Mouse Models of Parkinson’s Disease

Investigators report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with Parkinson’s disease brain protein extracts.
[Nature Communications]
Bengoa-Vergniory, N., Faggiani, E., Ramos-Gonzalez, P., Kirkiz, E., Connor-Robson, N., Brown, L. V., Siddique, I., Li, Z., Vingill, S., Cioroch, M., Cavaliere, F., Threlfell, S., Roberts, B., Schrader, T., Klärner, F.-G., Cragg, S., Dehay, B., Bitan, G., Matute, C., … Wade-Martins, R. (2020). CLR01 protects dopaminergic neurons in vitro and in mouse models of Parkinson’s disease. Nature Communications, 11(1), 4885. https://doi.org/10.1038/s41467-020-18689-x Cite
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Neuronal Defects in a Human Cellular Model of 22q11.2 Deletion Syndrome

Using electrophysiology and live imaging, the authors identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons.
[Nature Medicine]
Khan, T. A., Revah, O., Gordon, A., Yoon, S.-J., Krawisz, A. K., Goold, C., Sun, Y., Kim, C. H., Tian, Y., Li, M.-Y., Schaepe, J. M., Ikeda, K., Amin, N. D., Sakai, N., Yazawa, M., Kushan, L., Nishino, S., Porteus, M. H., Rapoport, J. L., … Paşca, S. P. (2020). Neuronal defects in a human cellular model of 22q11.2 deletion syndrome. Nature Medicine, 1–11. https://doi.org/10.1038/s41591-020-1043-9 Cite
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Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage

Scientists systematically investigated the expression profiles of 1,436 murine RNA-binding proteins in the developing mouse brain and identified quaking as a marker of the putative glial precursor cells population.
[Stem Cell Reports]
Takeuchi, A., Takahashi, Y., Iida, K., Hosokawa, M., Irie, K., Ito, M., Brown, J. B., Ohno, K., Nakashima, K., & Hagiwara, M. (2020). Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.08.010 Cite
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Insulin and Leptin/Upd2 Exert Opposing Influences on Synapse Number in Fat-Sensing Neurons

Researchers showed that under conditions of nutrient surplus, Upd2, a Drosophila leptin ortholog, regulated actin-based synapse reorganization to reduce bouton number in an inhibitory circuit, thus establishing a neural tone that was permissive for insulin release.
[Cell Metabolism]
Brent, A. E., & Rajan, A. (2020). Insulin and Leptin/Upd2 Exert Opposing Influences on Synapse Number in Fat-Sensing Neurons. Cell Metabolism, 0(0). https://doi.org/10.1016/j.cmet.2020.08.017 Cite
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Modeling the Function of BAX and BAK in Early Human Brain Development Using iPSC-Derived Systems

Scientists generated BAX/BAK double knockout human-induced pluripotent stem cells (hiPSCs), hiPSC-derived neural progenitor cells, neural rosettes, and cerebral organoids to uncover the effects of BAX and BAK deletion in an in vitro model of early human brain development.
[Cell Death & Disease]
Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems | Cell Death & Disease. (n.d.). Retrieved September 25, 2020, from https://www.nature.com/articles/s41419-020-03002-x Cite
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Regulation of Neuronal Commitment in Mouse Embryonic Stem Cells by the Reno1/Bahcc1 Locus

Scientists used RNA‐seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal differentiation.
[EMBO Reports]
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Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells

To understand transcriptomic differences in iPSC-derived monolayer neuronal cultures and 3D brain organoids, scientists differentiated eight human iPSC lines from healthy control subjects to generate cerebral organoids and cortical neuron monolayer cultures from the same set of iPSC lines.
[Stem Cells and Development]
Kathuria, A., Lopez-Lengowski, K., Watmuff, B., & Karmacharya, R. (2020). Comparative Transcriptomic Analysis of Cerebral Organoids and Cortical Neuron Cultures Derived from Human Induced Pluripotent Stem Cells. Stem Cells and Development. https://doi.org/10.1089/scd.2020.0069 Cite
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Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat

Adenoviral vectors carrying genes encoding vascular endothelial growth factor, glial cell-derived neurotrophic factor and neural cell adhesion molecule or gene engineered umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial cell-derived neurotrophic factor, and neural cell adhesion molecule were intrathecally injected before distal occlusion of the middle cerebral artery in rats.
[International Journal of Molecular Sciences]
Markosyan, V., Safiullov, Z., Izmailov, A., Fadeev, F., Sokolov, M., Kuznetsov, M., Trofimov, D., Kim, E., Kundakchyan, G., Gibadullin, A., Salafutdinov, I., Nurullin, L., Bashirov, F., & Islamov, R. (2020). Preventive Triple Gene Therapy Reduces the Negative Consequences of Ischemia-Induced Brain Injury after Modelling Stroke in a Rat. International Journal of Molecular Sciences, 21(18), 6858. https://doi.org/10.3390/ijms21186858 Cite
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