Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons
Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury SIRT2 has been suggested to exert effects opposite those of SIRT1, however...
| Authors: | ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2018 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/123908 |
| Online Access: | https://hdl.handle.net/2445/123908 |
| Access Level: | Open access |
| Keyword: | Mort cel·lular Neurones Malalties neurodegeneratives Cell death Neurons Neurodegenerative Diseases |
| _version_ | 1878736534886154240 |
|---|---|
| author | Romeo-Guitar, David |
| author2 | Leiva-Rodríguez, Tatiana Espinosa-Alcantud, María Sima Teruel, Núria Vaquero García, Alejandro Dominguez-Martín, Helena Ruano, Diego Casas, Caty |
| author2_role | author author author author author author author |
| author_browse | Casas, Caty Dominguez-Martín, Helena Espinosa-Alcantud, María Leiva-Rodríguez, Tatiana Romeo-Guitar, David Ruano, Diego Sima Teruel, Núria Vaquero García, Alejandro |
| author_facet | Romeo-Guitar, David Leiva-Rodríguez, Tatiana Espinosa-Alcantud, María Sima Teruel, Núria Vaquero García, Alejandro Dominguez-Martín, Helena Ruano, Diego Casas, Caty |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury SIRT2 has been suggested to exert effects opposite those of SIRT1, however, its roles in neurodegeneration and neuron response after nerve injury remain unclear Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IREI alpha and XBP1 by 21 days post injury Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged. MN survival To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells In this system, AK7 treatment of ER stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-kB and the consequent transcription of cytotoxic pro inflammatory factors similarly The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_90b7d9ee519e4ac49341c84631f7dbf1 |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/123908 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | Nature Publishing Group |
| publisherStr | Nature Publishing Group |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons Romeo-Guitar, David Leiva-Rodríguez, Tatiana Espinosa-Alcantud, María Sima Teruel, Núria Vaquero García, Alejandro Dominguez-Martín, Helena Ruano, Diego Casas, Caty Mort cel·lular Neurones Malalties neurodegeneratives Cell death Neurons Neurodegenerative Diseases Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury SIRT2 has been suggested to exert effects opposite those of SIRT1, however, its roles in neurodegeneration and neuron response after nerve injury remain unclear Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IREI alpha and XBP1 by 21 days post injury Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged. MN survival To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells In this system, AK7 treatment of ER stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-kB and the consequent transcription of cytotoxic pro inflammatory factors similarly The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment. Nature Publishing Group https://hdl.handle.net/2445/123908 |
| spellingShingle | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons Romeo-Guitar, David Mort cel·lular Neurones Malalties neurodegeneratives Cell death Neurons Neurodegenerative Diseases |
| status_str | publishedVersion |
| title | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| title_full | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| title_fullStr | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| title_full_unstemmed | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| title_short | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| title_sort | Sirt1 Activation With Neuroheal Is Neuroprotective But Sirt2 Inhibition With Ak7 Is Detrimental For Disconnected Motoneurons |
| topic | Mort cel·lular Neurones Malalties neurodegeneratives Cell death Neurons Neurodegenerative Diseases |
| topic_facet | Mort cel·lular Neurones Malalties neurodegeneratives Cell death Neurons Neurodegenerative Diseases |
| url | https://hdl.handle.net/2445/123908 |