Growth-Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man.


Journal

Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 16 10 2019
accepted: 20 02 2020
pubmed: 17 3 2020
medline: 22 6 2021
entrez: 16 3 2020
Statut: ppublish

Résumé

Neurons of the central nervous system (CNS) that project long axons into the spinal cord have a poor axon regenerative capacity compared to neurons of the peripheral nervous system. The corticospinal tract (CST) is particularly notorious for its poor regeneration. Because of this, traumatic spinal cord injury (SCI) is a devastating condition that remains as yet uncured. Based on our recent observations that direct neuronal interleukin-4 (IL-4) signaling leads to repair of axonal swellings and beneficial effects in neuroinflammation, we hypothesized that IL-4 acts directly on the CST. Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Most importantly, IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.

Identifiants

pubmed: 32172457
doi: 10.1007/s10571-020-00820-7
pii: 10.1007/s10571-020-00820-7
pmc: PMC7497511
doi:

Substances chimiques

PTEN Phosphohydrolase EC 3.1.3.67

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1327-1338

Subventions

Organisme : Progressive MS alliance
ID : PA-1604-08492
Organisme : Gemeinnützige Hertie-Stiftung
ID : P1180009
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC-TR-128
Organisme : Deutsche Forschungsgemeinschaft
ID : CRC1080

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Auteurs

Nicholas Hanuscheck (N)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Andrea Schnatz (A)

Institute for Developmental Biology and Neurobiology, Molecular Cell Biology, Johannes Gutenberg University Mainz, 55099, Mainz, Germany.

Carine Thalman (C)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Steffen Lerch (S)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Yvonne Gärtner (Y)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Micaela Domingues (M)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Lynn Bitar (L)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Robert Nitsch (R)

University Medical Center, Institute for Translational Neuroscience, Westfälische Wilhelms-University Münster, Albert-Schweitzer-Campus, 48149, Münster, Germany.

Frauke Zipp (F)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany.

Christina F Vogelaar (CF)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131, Mainz, Germany. tineke.vogelaar@unimedizin-mainz.de.

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