Cerebrospinal Fluid from Patients with Sporadic Amyotrophic Lateral Sclerosis Induces Degeneration of Motor Neurons Derived from Human Embryonic Stem Cells

Rajendrarao Sumitha, Venkataswamy M. Manjunatha, Rajesh K. Sabitha, Phalguni A. Alladi, A. Nalini, Laxmi T. Rao, B. K. Chandrasekhar Sagar, Harry W. M. Steinbusch, Boris W. Kramer, T. N. Sathyaprabha, Trichur R. Raju*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Disease modeling has become challenging in the context of amyotrophic lateral sclerosis (ALS), as obtaining viable spinal motor neurons from postmortem patient tissue is an unlikely possibility. Limitations in the animal models due to their phylogenetic distance from human species hamper the success of translating possible findings into therapeutic options. Accordingly, there is a need for developing humanized models as a lead towards identifying successful therapeutic possibilities. In this study, human embryonic stem cellsBJNHem20were differentiated into motor neurons expressing HB9, Islet1, and choline acetyl transferase using retinoic acid and purmorphamine. These motor neurons discharged spontaneous action potentials with two different frequencies (5Hz), and majority of them were principal neurons firing with

Original languageEnglish
Pages (from-to)1014-1034
Number of pages21
JournalMolecular Neurobiology
Volume56
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Amyotrophic lateral sclerosis
  • Motor neurons
  • Human embryonic stem cells
  • Cerebrospinal fluid
  • TRANSGENIC MOUSE MODEL
  • MICROTUBULE-ASSOCIATED PROTEINS
  • CU,ZN SUPEROXIDE-DISMUTASE
  • BDNF MESSENGER-RNA
  • SPINAL-CORD
  • GOLGI-APPARATUS
  • CORTICAL HYPEREXCITABILITY
  • RESPIRATORY-CHAIN
  • ER STRESS
  • NEUROFILAMENT PHOSPHORYLATION

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