@article{c74005d8c56f4d50ab1605eaede83a3d,
title = "Cerebrospinal Fluid from Patients with Sporadic Amyotrophic Lateral Sclerosis Induces Degeneration of Motor Neurons Derived from Human Embryonic Stem Cells",
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",
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",
author = "Rajendrarao Sumitha and Manjunatha, {Venkataswamy M.} and Sabitha, {Rajesh K.} and Alladi, {Phalguni A.} and A. Nalini and Rao, {Laxmi T.} and Sagar, {B. K. Chandrasekhar} and Steinbusch, {Harry W. M.} and Kramer, {Boris W.} and Sathyaprabha, {T. N.} and Raju, {Trichur R.}",
note = "Funding Information: We are grateful to Prof. Inamdar, JNCASR, for providing the human embryonic stem cell line-BJNHem20. We are thankful to Ms. Jessena Ponmalar for her assistance in conducting mitochondrial assays and Dr. Mariamma Philip for the statistical analysis related to electrophysiology experiments. Funding Information: spontaneous action potentials. ALS-CSF exposure for 48 h induced degenerative changes such as organelle dysfunction, reduced BDNF expression, altered expression of cytoskeletal proteins, and increased phosphorylation of neurofilaments and hyperexcitability. Such changes along with the increased expression of pro-apoptotic molecules culminated in the death of motor neurons. These results conform to the neurodegenerative changes observed in our earlier studies in rodent models of sporadic ALS Funding Information This study was supported by National Institute of Mental Health and Neurosciences, Bengaluru, India. Senior Research Fellowship for SR was funded by Indian Council of Medical Research (ICMR) (File No. 81/03/2013/SCRT/BMS). Publisher Copyright: {\textcopyright} 2018, Springer Science+Business Media, LLC, part of Springer Nature.",
year = "2019",
month = feb,
doi = "10.1007/s12035-018-1149-y",
language = "English",
volume = "56",
pages = "1014--1034",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Springer, Cham",
number = "2",
}