Publicação
Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity
| Resumo: | Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP<sub>3</sub>R2-Ca<sup>2+</sup>-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation. |
|---|---|
| Autores principais: | Bravo, Joana |
| Outros Autores: | Ribeiro, Inês Moreira; Terceiro, Ana Filipa; Andrade, Elva B.; Portugal, Camila Cabral; Lopes, Igor M.; Azevedo, Maria M.; Sousa, Mafalda; Lopes, Cátia D. F.; Lobo, Andrea C.; Canedo, Teresa; Relvas, João Bettencourt; Summavielle, Teresa |
| Assunto: | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866877665370177536 |
|---|---|
| author | Bravo, Joana |
| author2 | Ribeiro, Inês Moreira Terceiro, Ana Filipa Andrade, Elva B. Portugal, Camila Cabral Lopes, Igor M. Azevedo, Maria M. Sousa, Mafalda Lopes, Cátia D. F. Lobo, Andrea C. Canedo, Teresa Relvas, João Bettencourt Summavielle, Teresa |
| author2_role | author author author author author author author author author author author author |
| author_facet | Bravo, Joana Ribeiro, Inês Moreira Terceiro, Ana Filipa Andrade, Elva B. Portugal, Camila Cabral Lopes, Igor M. Azevedo, Maria M. Sousa, Mafalda Lopes, Cátia D. F. Lobo, Andrea C. Canedo, Teresa Relvas, João Bettencourt Summavielle, Teresa |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Bravo, Joana\"},{\"Person.name\":\"Ribeiro, Inês Moreira\"},{\"Person.name\":\"Terceiro, Ana Filipa\"},{\"Person.name\":\"Andrade, Elva B.\"},{\"Person.name\":\"Portugal, Camila Cabral\"},{\"Person.name\":\"Lopes, Igor M.\"},{\"Person.name\":\"Azevedo, Maria M.\"},{\"Person.name\":\"Sousa, Mafalda\"},{\"Person.name\":\"Lopes, Cátia D. F.\"},{\"Person.name\":\"Lobo, Andrea C.\"},{\"Person.name\":\"Canedo, Teresa\"},{\"Person.name\":\"Relvas, João Bettencourt\"},{\"Person.name\":\"Summavielle, Teresa\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Bravo, Joana Ribeiro, Inês Moreira Terceiro, Ana Filipa Andrade, Elva B. Portugal, Camila Cabral Lopes, Igor M. Azevedo, Maria M. Sousa, Mafalda Lopes, Cátia D. F. Lobo, Andrea C. Canedo, Teresa Relvas, João Bettencourt Summavielle, Teresa |
| datacite.date.Accepted.fl_str_mv | 2022-01-21T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-06-13T09:18:02Z |
| datacite.date.embargoed.fl_str_mv | 2022-06-13T09:18:02Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| datacite.titles.title.fl_str_mv | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Bravo, Joana Ribeiro, Inês Moreira Terceiro, Ana Filipa Andrade, Elva B. Portugal, Camila Cabral Lopes, Igor M. Azevedo, Maria M. Sousa, Mafalda Lopes, Cátia D. F. Lobo, Andrea C. Canedo, Teresa Relvas, João Bettencourt Summavielle, Teresa |
| dc.date.Accepted.fl_str_mv | 2022-01-21T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-06-13T09:18:02Z |
| dc.date.embargoed.fl_str_mv | 2022-06-13T09:18:02Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/78349 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| dc.title.fl_str_mv | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP<sub>3</sub>R2-Ca<sup>2+</sup>-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://prod-dspace.uminho.pt/bitstreams/8f8dd91e-ce11-455c-bc0b-c4a25072df77/download |
| id | rum_e71be0a4e580f30cd7259e2fd60f9239 |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/78349 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/78349 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Bravo, Joana Ribeiro, Inês Moreira Terceiro, Ana Filipa Andrade, Elva B. Portugal, Camila Cabral Lopes, Igor M. Azevedo, Maria M. Sousa, Mafalda Lopes, Cátia D. F. Lobo, Andrea C. Canedo, Teresa Relvas, João Bettencourt Summavielle, Teresa |
| publishDate | 2022 |
| publisher.none.fl_str_mv | Multidisciplinary Digital Publishing Institute (MDPI) |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engMultidisciplinary Digital Publishing Institute (MDPI)porExposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP<sub>3</sub>R2-Ca<sup>2+</sup>-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.application/pdfporNeuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticityBravo, JoanaRibeiro, Inês MoreiraTerceiro, Ana FilipaAndrade, Elva B.Portugal, Camila CabralLopes, Igor M.Azevedo, Maria M.Sousa, MafaldaLopes, Cátia D. F.Lobo, Andrea C.Canedo, TeresaRelvas, João BettencourtSummavielle, TeresaHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptDOIIsPartOf10.3390/cells110303552022-06-13T09:18:02Z2022-01-212022-02-11T14:46:27Z2022-01-21T00:00:00ZHandlehttps://hdl.handle.net/1822/78349http://purl.org/coar/access_right/c_abf2open accessMethamphetamineNeuron-to-microgliaNeuroprotectionContact-dependentCD200PSD9522594242 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2022-01-21http://creativecommons.org/licenses/by/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://prod-dspace.uminho.pt/bitstreams/8f8dd91e-ce11-455c-bc0b-c4a25072df77/download |
| spellingShingle | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity Bravo, Joana Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| status | SINGLETON |
| subject.fl_str_mv | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| title | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| title_full | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| title_fullStr | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| title_full_unstemmed | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| title_short | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| title_sort | Neuron-microglia contact-dependent mechanisms attenuate methamphetamine-induced microglia reactivity and enhance neuronal plasticity |
| topic | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| topic_facet | Methamphetamine Neuron-to-microglia Neuroprotection Contact-dependent CD200 PSD95 |
| url | https://hdl.handle.net/1822/78349 |
| visible | 1 |