Neuregulin 1 Reduces Motoneuron Cell Death and Promotes Neurite Growth in an in Vitro Model of Motoneuron Degeneration
Mòdol Caballero, Guillem (Universitat Autònoma de Barcelona. Institut de Neurociències)
Santos, Daniel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Navarro, X. (Xavier) (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Herrando-Grabulosa, Mireia (Universitat Autònoma de Barcelona. Institut de Neurociències)

Fecha:	2018
Resumen:	Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with no effective treatment currently available. Although the mechanisms of motoneuron (MN) death are still unclear, glutamate excitotoxicity and neuroinflammatory reaction are two main features in the neurodegenerative process of ALS. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and neuromuscular junctions. Several recent evidences suggest that NRG1 and their ErbB receptors are involved in ALS. However, further knowledge is still needed to clarify the role of the NRG1-ErbB pathway on MN survival. In this study we used an in vitro model of spinal cord organotypic cultures (SCOCs) subject to chronic excitotoxicity caused by DL- threo -β-hydroxyaspartic acid (THA) to characterize the effect of NRG1 on MN survival. Our results show that addition of recombinant human NRG1 (rhNRG1) to the medium significantly increased MN survival through the activation of ErbB receptors which was ablated with lapatinib (LP), an ErbB inhibitor, and reduced microglial reactivity overcoming the excitotoxicity effects. rhNRG1 activated the pro-survival PI3K/AKT pathway and restored the autophagic flux in the spinal cord culture. Moreover, addition of rhNRG1 to the medium promoted motor and sensory neurite outgrowth. These findings indicate that increasing NRG1 at the spinal cord is an interesting approach for promoting MN protection and regeneration.
Ayudas:	Instituto de Salud Carlos III RD16-0011-0014
Nota:	Altres ajuts: This work was supported by grant TV3201428-10 of Fundació la Marató de TV3, grant #20289 of AFM-Téléthon, cooperative project 2015-01 from CIBERNED.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Neuregulin 1 ; ErbB receptors ; Motoneuron ; Excitotoxicity ; Spinal cord ; Organotypic culture ; Amyotrophic lateral sclerosis ; Neurite growth
Publicado en:	Frontiers in cellular neuroscience, Vol. 11 (january 2018) , ISSN 1662-5102

DOI: 10.3389/fncel.2017.00431
PMID: 29375317

11 p, 4.2 MB

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