ALS-related human cortical and motor neurons survival is differentially affected by Sema3A article

Anastasya Birger, Miri Ottolenghi, Liat Perez, Benjamin Reubinoff*, Oded Behar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by cell death of upper and lower motor neurons (MNs). The cause of MN cell loss is not completely understood but involves both cell autonomous and non-cell autonomous mechanisms. Numerous molecules have been implicated to be involved in the death of MNs. One such candidate is semaphorin 3A (Sema3A). In ALS patients, Sema3A was shown to be significantly upregulated in the motor cortex and downregulated in the spinal cord. In the mouse, Sema3A was shown to be an axon repellent molecule for MNs. Sema3A could also induce death of different neuronal types that are also repelled by it, including sensory, sympathetic, retinal, and cortical neurons. In contrast, astrocyte-specific knockout of Sema3A results in motor neuron cell death, consistent with the idea that Sema3A is a survival factor for mouse motor neurons. Here, we tested the response of human cortical neurons and spinal cord MNs to Sema3A. We found that Sema3A enhances the survival of spinal cord MNs. In contrast, Sema3A reduces the survival of cortical neurons. Thus, both upregulation of Sema3A in the cortex, or downregulation in the spinal cord of ALS patients is likely to directly contribute to MNs cell loss in ALS patients.

Original languageAmerican English
Article number256
JournalCell Death and Disease
Volume9
Issue number3
DOIs
StatePublished - 1 Mar 2018

Bibliographical note

Funding Information:
We are grateful to Dr. Kevin C. Eggan for kindly providing us the HB9-GFP hESC line. We would also like to thank Dr. Michal Gropp for comments on the manuscript. This work was supported by a grant from Legacy Heritage Biomedical Science Partnership (Grant No. 1306/10, O.B. and B.R.), the Israel Science Foundation Grant No. 947/14, O.B.) and by a donation from Judy and Sydney Swartz (B.R.).

Publisher Copyright:
© 2018 The Author(s).

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