TY - JOUR
T1 - Cerebrospinal Fluid from Patients with Sporadic Amyotrophic Lateral Sclerosis Induces Degeneration of Motor Neurons Derived from Human Embryonic Stem Cells
AU - Sumitha, Rajendrarao
AU - Manjunatha, Venkataswamy M.
AU - Sabitha, Rajesh K.
AU - Alladi, Phalguni A.
AU - Nalini, A.
AU - Rao, Laxmi T.
AU - Sagar, B. K. Chandrasekhar
AU - Steinbusch, Harry W. M.
AU - Kramer, Boris W.
AU - Sathyaprabha, T. N.
AU - Raju, Trichur R.
N1 - 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:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/2
Y1 - 2019/2
N2 - 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
AB - 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
KW - Amyotrophic lateral sclerosis
KW - Motor neurons
KW - Human embryonic stem cells
KW - Cerebrospinal fluid
KW - TRANSGENIC MOUSE MODEL
KW - MICROTUBULE-ASSOCIATED PROTEINS
KW - CU,ZN SUPEROXIDE-DISMUTASE
KW - BDNF MESSENGER-RNA
KW - SPINAL-CORD
KW - GOLGI-APPARATUS
KW - CORTICAL HYPEREXCITABILITY
KW - RESPIRATORY-CHAIN
KW - ER STRESS
KW - NEUROFILAMENT PHOSPHORYLATION
U2 - 10.1007/s12035-018-1149-y
DO - 10.1007/s12035-018-1149-y
M3 - Article
C2 - 29858777
SN - 0893-7648
VL - 56
SP - 1014
EP - 1034
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 2
ER -