{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:15:51Z","timestamp":1777014951321,"version":"3.51.4"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2008,6,26]],"date-time":"2008-06-26T00:00:00Z","timestamp":1214438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor necrosis factor (TNF)-\u03b1 has been reported to modulate brain injury, but remarkably, little is known about its effects on neurogenesis. We report that TNF-\u03b1 strongly influences survival, proliferation, and neuronal differentiation in cultured subventricular zone (SVZ) neural stem\/progenitor cells derived from the neonatal P1\u20133 C57BL\/6 mice. By using single-cell calcium imaging, we developed a method, based on cellular response to KCl and\/or histamine, that allows the functional evaluation of neuronal differentiation. Exposure of SVZ cultures to 1 and 10 ng\/ml mouse or 1 ng\/ml human recombinant TNF-\u03b1 resulted in increased differentiation of cells displaying a neuronal-like profile of [Ca2+]i responses, compared with the predominant profile of immature cells observed in control, nontreated cultures. Moreover, by using neutralizing antibodies for each TNF-\u03b1 receptor, we found that the proneurogenic effect of 1 ng\/ml TNF-\u03b1 is mediated via tumor necrosis factor receptor 1 activation. Accordingly, the percentage of neuronal nuclear protein-positive neurons was increased following exposure to mouse TNF-\u03b1. Interestingly, exposure of SVZ cultures to 1 ng\/ml TNF-\u03b1 induced cell proliferation, whereas 10 and 100 ng\/ml TNF-\u03b1 induced apoptotic cell death. Moreover, we found that exposure of SVZ cells to TNF-\u03b1 for 15 minutes or 6 hours caused an increase in the phospho-stress-activated protein kinase\/c-Jun N-terminal kinase immunoreactivity initially in the nucleus and then in growing axons, colocalizing with tau, consistent with axonogenesis. Taken together, these results show that TNF-\u03b1 induces neurogenesis in neonatal SVZ cell cultures of mice. TNF-\u03b1, a proinflammatory cytokine and a proneurogenic factor, may play a central role in promoting neurogenesis and brain repair in response to brain injury and infection.<\/jats:p>\n                  <jats:p>Disclosure of potential conflicts of interest is found at the end of this article.<\/jats:p>","DOI":"10.1634\/stemcells.2007-0914","type":"journal-article","created":{"date-parts":[[2008,6,26]],"date-time":"2008-06-26T21:23:45Z","timestamp":1214515425000},"page":"2361-2371","source":"Crossref","is-referenced-by-count":179,"title":["Tumor Necrosis Factor-\u03b1 Modulates Survival, Proliferation, and Neuronal Differentiation in Neonatal Subventricular Zone Cell Cultures"],"prefix":"10.1093","volume":"26","author":[{"given":"Liliana","family":"Bernardino","sequence":"first","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Fabienne","family":"Agasse","sequence":"additional","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Bruno","family":"Silva","sequence":"additional","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Raquel","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Sofia","family":"Grade","sequence":"additional","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Jo\u00e3o O.","family":"Malva","sequence":"additional","affiliation":[{"name":"Neuroprotection and Neurogenesis in Brain Repair Group, Center for Neuroscience and Cell Biology, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2008,6,26]]},"reference":[{"key":"2022011315204423000_bib1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0896-6273(93)90281-U","article-title":"Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone","volume":"11","author":"Luskin","year":"1993","journal-title":"Neuron"},{"key":"2022011315204423000_bib2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0092-8674(00)80783-7","article-title":"Subventricular zone astrocytes are neural stem cells 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