{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:40:19Z","timestamp":1771627219615,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T00:00:00Z","timestamp":1642723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/SAU-TOX\/30647\/2017"],"award-info":[{"award-number":["PTDC\/SAU-TOX\/30647\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020"],"award-info":[{"award-number":["UIDB\/04293\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\/IP3R2-Ca2+-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.<\/jats:p>","DOI":"10.3390\/cells11030355","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T08:37:18Z","timestamp":1642754238000},"page":"355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Neuron\u2013Microglia Contact-Dependent Mechanisms Attenuate Methamphetamine-Induced Microglia Reactivity and Enhance Neuronal Plasticity"],"prefix":"10.3390","volume":"11","author":[{"given":"Joana","family":"Bravo","sequence":"first","affiliation":[{"name":"Addiction Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto (UP), 4050-313 Porto, Portugal"},{"name":"Escola Superior de Sa\u00fade, Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4923-3599","authenticated-orcid":false,"given":"In\u00eas","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, 4806-909 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Ana Filipa","family":"Terceiro","sequence":"additional","affiliation":[{"name":"Addiction Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto (UP), 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1941-580X","authenticated-orcid":false,"given":"Elva B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto (UP), 4050-313 Porto, Portugal"},{"name":"Escola Superior de Sa\u00fade, Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"},{"name":"Immunobiology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-6545","authenticated-orcid":false,"given":"Camila Cabral","family":"Portugal","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Glial Cell Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-2711","authenticated-orcid":false,"given":"Igor M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Laboratory Animal Science, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"given":"Maria M.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Advanced Light Microscopy Scientific Platform, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-1070","authenticated-orcid":false,"given":"Mafalda","family":"Sousa","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Advanced Light Microscopy Scientific Platform, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"given":"C\u00e1tia D. F.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Molecular Bionics Group\u2014Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona, Spain"}]},{"given":"Andrea C.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Addiction Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-153X","authenticated-orcid":false,"given":"Teresa","family":"Canedo","sequence":"additional","affiliation":[{"name":"Addiction Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"FMUP\u2014Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Jo\u00e3o Bettencourt","family":"Relvas","sequence":"additional","affiliation":[{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Glial Cell Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"FMUP\u2014Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2548-6281","authenticated-orcid":false,"given":"Teresa","family":"Summavielle","sequence":"additional","affiliation":[{"name":"Addiction Biology, i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"IBMC\u2014Instituto de Biologia Molecular e Celular, Universidade do Porto (UP), 4200-135 Porto, Portugal"},{"name":"Escola Superior de Sa\u00fade, Polit\u00e9cnico do Porto, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuron.2019.01.016","article-title":"The Molecular Basis of Drug Addiction: Linking Epigenetic to Synaptic and Circuit Mechanisms","volume":"102","author":"Nestler","year":"2019","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.brainresrev.2009.03.002","article-title":"Methamphetamine toxicity and messengers of death","volume":"60","author":"Krasnova","year":"2009","journal-title":"Brain Res. 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