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Cytokines released by the maternal immune system can cross the placenta and enter fetal circulation. In the fetal brain, embryonic microglia may produce additional cytokines and other inflammatory mediators in response to maternally derived cytokines. This resulting cytokine imbalance is suggested to impair neurogenesis and brain development, potentially contributing to the onset of neuropsychiatric disorders in offspring. To investigate microglial involvement in neurogenesis under pathological conditions, we used the spontaneously immortalized microglial cell line (SIM-A9), and confirmed the expression of Iba1 and CD68 via immunocytochemistry. Additionally, SIM-A9 cells expressed CX3CR1, Ki67, and isolectin. Upon Poly I:C stimulation, SIM-A9 cells released the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-\u03b1), as well as nitric oxide (NO), as determined by ELISA and Griess assay, respectively. After confirming SIM-A9 cell activation by Poly I:C, we co-cultured these cells with neural stem\/progenitor cells (NSPCs) from embryonic mouse neocortex using a transwell system. We examined how chronically activated microglia influence NSPC differentiation and characterized the resulting cell phenotypes using immunocytochemistry. Our results demonstrate that SIM-A9 cells support NSPC differentiation into neurons as early as three days in culture. However, the number of neurons decreased with prolonged culture. Furthermore, Poly I:C in the NSPC culture media, as well as cytokines secreted by Poly I:C-activated SIM-A9 cells, showed a supportive effect on astrocyte differentiation.<\/jats:p>","DOI":"10.1007\/s11626-025-01091-6","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:23:23Z","timestamp":1759249403000},"page":"991-1004","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A co-culture system to study the effects of Poly I:C-activated microglia on the differentiation of murine primary neural stem cells"],"prefix":"10.1007","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0411-9634","authenticated-orcid":false,"given":"Marie Pierre","family":"Manitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Violou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Hedst\u00fcck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"B\u00f6sing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kottmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Freund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Juckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"issue":"26","key":"1091_CR1","doi-asserted-by":"publisher","first-page":"15983","DOI":"10.1073\/pnas.2237050100","volume":"100","author":"J Aarum","year":"2003","unstructured":"Aarum J, Sandberg K, Haeberlein SL, Persson MA (2003) Migration and differentiation of neural precursor cells can be directed by microglia. 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