Activation of neonatal microglia can be influenced by other neural cells
Open accessAbstract
During development, microglial progenitor cells migrate into the brain from the periphery, a process critical to the maturation of the developing brain. Although they perform functions similar to mature, adult microglia, immature microglia are distinct from mature microglia. Activation of immature microglia, via an early-life immune challenge, can lead to persistent changes in microglial function, resulting in long-term neuronal and cognitive dysfunction. Early-life immune activation is associated with multiple neurodevelopmental disorders, including autism, ADHD, schizophrenia, and cerebral palsy - disorders with known or suspected immune etiologies, and strong sex biases for males. Activation of immature microglia requires further examination to determine its potential role in these neurodevelopmental disorders. More work is also necessary to better understand the relationship between developing microglia and other developing neural cells during this critical period of development. Thus, we treated freshly isolated, sex-specific microglia from the rat hippocampus with lipopolysaccharide (LPS) on P4, in either the presence or absence of other neural cells. Mixed and microglial-specific cultures were analyzed for inflammatory gene expression to determine whether immature microglia exhibited a sex-specific response to immune activation, and if the presence of all other neural cells influenced that response. We found that the microglial response to an LPS-induced immune activation differed depending on the presence of other neural cells in the culture. We found very few sex differences in the cytokine response, except that the microglial expression of IL-6 following immune activation was more robust in male microglia that were in the presence of other neural cells than female microglia in the same condition.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Male, but not female, offspring of exposed mice exhibited elevated IL-6 cytokine levels and repetitive-restricted behaviours compared with sex-matched offspring of control mice.
“For example, male, but not female, offspring of exposed mice exhibited elevated IL-6 cytokine levels and repetitive-restricted behaviours compared with sex-matched offspring of control mice288–290.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [290]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Immune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766 · see citing works
Lehnardt, S., Lachance, C., Patrizi, S., Lefebvre, S., Follett, P. L., Jensen, F. E., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02478.2002 · Cited by 684 · see citing works
Sex differences in microglial colonization of the developing rat brain
Schwarz, J. M., Sholar, P. W., & Bilbo, S. D. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07630.x · Cited by 672 · see citing works
Self-citationImmune proteins in brain development and synaptic plasticity
Boulanger, L. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.001 · Cited by 555 · see citing works
Microglia Are Essential to Masculinization of Brain and Behavior
Lenz, K. M., Nugent, B. M., Haliyur, R., & McCarthy, M. M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1268-12.2013 · Cited by 526 · see citing works
The impact of systemic infection on the progression of neurodegenerative disease
Perry, V. H., Newman, T. A., & Cunningham, C. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1032 · Cited by 428 · see citing works
The origin and differentiation of microglial cells during development
Cuadros, M. Á. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00035-5 · Cited by 305 · see citing works
Liu, W., Tang, Y., & Feng, J. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.05.011 · Cited by 303 · cited 1× · see citing works
“Stimulated microglia can directly activate astrocytes, which go on to generate a calcium wave that spreads to local and distant microglia to further excite or inhibit microglial activity [14].”
BackgroundNeuroinflammation and microglia: considerations and approaches for neurotoxicity assessment
Harry, G. J., & Kraft, A. D. (2008) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.4.10.1265 · Cited by 292 · see citing works
Sex Differences in the Brain, Behavior, and Neuropsychiatric Disorders
Bao, A., & Swaab, D. F. (2010) · The Neuroscientist · doi:10.1177/1073858410377005 · Cited by 225 · see citing works
Garay, P. (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00136 · Cited by 217 · see citing works
Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats
Loram, L. C., Sholar, P. W., Taylor, F. R., Wiesler, J. L., Babb, J. A., Strand, K. A., Berkelhammer, D. L., Day, H. E. W., Maier, S. F., & Watkins, L. R. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.02.018 · Cited by 196 · see citing works
Cerciat, M., Unkila, M., García‐Segura, L. M., & Arévalo, M. (2009) · Glia · doi:10.1002/glia.20904 · Cited by 160 · see citing works
Control of GABA release at single mossy fiber-CA3 connections in the developing hippocampus
Safiulina (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/neuro.19.001.2010 · Cited by 124 · see citing works
Microglial regulation of immunological and neuroprotective functions of astroglia
Chen, S., Oyarzabal, E. A., Sung, Y.-F., Chu, C., Wang, Q., Chen, S.-L., Lu, R., & Hong, J.-S. (2014) · Glia · doi:10.1002/glia.22738 · Cited by 115 · see citing works
Hung, J., Chansard, M., Ousman, S., Nguyen, M., & Colicos, M. A. (2010) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2009.06.150 · Cited by 32 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function
Lenz, K. M., & Nelson, L. H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00698 · Cited by 491 · see citing works
Sex differences in autism spectrum disorder: a review
Ferri, S. L., Abel, T., & Brodkin, E. S. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0874-2 · Cited by 392 · see citing works
Sex and gender in neurodevelopmental conditions
Bölte, S., Neufeld, J., Marschik, P. B., Williams, Z. J., Gallagher, L., & Lai, M.-C. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00774-6 · Cited by 249 · see citing works
Sex differences in the neuroimmune system
Osborne, B. F., Turano, A., & Schwarz, J. M. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.05.007 · Cited by 90 · see citing works
Self-citationPlacental Macrophages: A Window Into Fetal Microglial Function in Maternal Obesity
Edlow, A. G., Glass, R. M., Smith, C. J. W., Tran, P. K., James, K. E., & Bilbo, S. D. (2018) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2018.11.004 · Cited by 84 · see citing works
Microglia and sexual differentiation of the developing brain: A focus on extrinsic factors
VanRyzin, J. W., Marquardt, A. E., Pickett, L. A., & McCarthy, M. M. (2019) · Glia · doi:10.1002/glia.23740 · Cited by 81 · see citing works
Ardalan, M., Chumak, T., Vexler, Z. S., & Mallard, C. E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092270 · Cited by 79 · see citing works
The role of microglia in neuropsychiatric disorders and suicide
Brisch, R., Wojtylak, S., Saniotis, A., Steiner, J. H., Gos, T., Kumaratilake, J., Henneberg, M., & Wolf, R. J. (2021) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-021-01334-z · Cited by 71 · see citing works
Nelson, L. H., Saulsbery, A. I., & Lenz, K. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.002 · Cited by 61 · see citing works
Pramotton, F. M., Spitz, S., & Kamm, R. D. (2024) · Advanced Science · doi:10.1002/advs.202403892 · Cited by 33 · see citing works
mGlu3 receptor regulates microglial cell reactivity in neonatal rats
Zinni, M., Mairesse, J., Pansiot, J., Fazio, F., Iacovelli, L., Antenucci, N., Orlando, R., Nicoletti, F., Vaiman, D., & Baud, O. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02049-z · Cited by 28 · see citing works
Candidiasis of the Central Nervous System in Neonates and Children With Primary Immunodeficiencies
Drummond, R. A., & Lionakis, M. S. (2018) · Current Fungal Infection Reports · doi:10.1007/s12281-018-0316-y · Cited by 23 · see citing works
Sex- and Development-Dependent Responses of Rat Microglia to Pro- and Anti-inflammatory Stimulation
Lively, S. S., Wong, R., Lam, D., & Schlichter, L. C. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00433 · Cited by 20 · see citing works
Hoshi, T., Toyama, T., Shinozaki, Y., Koizumi, S., Lee, J., Naganuma, A., & Hwang, G. (2019) · The Journal of Toxicological Sciences · doi:10.2131/jts.44.471 · Cited by 19 · see citing works
Microglia Regulate Cell Genesis in a Sex-dependent Manner in the Neonatal Hippocampus
Nelson, L. H., Peketi, P., & Lenz, K. M. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.10.009 · Cited by 19 · see citing works
Carroll, J. A., Race, B., Williams, K., Striebel, J. F., & Chesebro, B. W. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02240-w · Cited by 17 · see citing works
Dieu‐Lugon, B. L., Dupré, N., Legouez, L., Leroux, P., Gonzalez, B. J., Marret, S., Leroux‐Nicollet, I., & Cléren, C. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14664 · Cited by 11 · see citing works
Turano, A., McAuley, E. M., Muench, M. C., & Schwarz, J. M. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113449 · Cited by 11 · see citing works
Self-citationKozareva, D. A., Moloney, G. M., Hoban, A. E., Rossini, V., Nally, K., Cryan, J. F., & Nolan, Y. M. (2019) · Neuronal Signaling · doi:10.1042/ns20180177 · Cited by 11 · see citing works
Method of Microglial DNA-RNA Purification from a Single Brain of an Adult Mouse
Raihan, M. O., McGregor, B. A., Velaris, N. A., Brishti, A., Hur, J., & Porter, J. E. (2021) · Methods and Protocols · doi:10.3390/mps4040086 · Cited by 8 · see citing works
Autism-Like Behavior in the Offspring of CYP11A1-Overexpressing Pregnant Rats
Pan, T., Jiang, C., Cheng, J., Xie, J., Liu, X., Xu, W., & He, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.774439 · Cited by 8 · see citing works
Walker, K. A., Rhodes, S. T., Liberman, D. A., Gore, A. C., & Bell, M. R. (2024) · NeuroToxicology · doi:10.1016/j.neuro.2024.07.009 · Cited by 7 · see citing works
Schwarz, J. M. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.04.008 · Cited by 7 · see citing works
Self-citationde Albuquerque, G. L., Manhães‐de‐Castro, R., Lacerda, D. C., Calado, C. M. S. D. S., de Morais, A. T. B., Visco, D. B., Manhães-de-Castro, F. M., & Toscano, A. E. (2023) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2022-0463 · Cited by 3 · see citing works
Hedley, K. E., Gomez, H. M., Kecelioglu, E. D., Carroll, O. R., Jobling, P., Horvat, J. C., & Tadros, M. A. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03150-3 · Cited by 2 · see citing works
Allen, J., Isaza-Correa, J. M., Kelly, L. A., Melo, A. M., Power, C., Mahony, A., McDonald, D., & Molloy, E. J. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1567221 · Cited by 1 · see citing works
Effects of a highly simplified microbiota on postnatal intestinal, immune, and brain development
Sturgeon, H., Castillo‐Ruiz, A., Ukpong, E., Praveen, L., Leyva, G., Chassaing, B., & Forger, N. G. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106085 · Cited by 1 · see citing works
Age-relevant in vitro models may lead to improved translational research for traumatic brain injury
Dickerson, M. R., Correa, F. G., Boni, J. L., & VandeVord, P. J. (2022) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2022.100391
Guo, C., Zhou, F., Qin, C., Zhang, X., Chang, H., & Zhao, X. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261465846
- Authors
- Turano, A., Lawrence, J. H., & Schwarz, J. M.
- Affiliations
- University of Delaware (US)
- Corresponding author
- Turano, Alexandra
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 657
- Pages
- 32-37
- ISSN
- 0304-3940 (ISSN-L)
- PMC
- PMC5594748
- OpenAlex
- W2741916734
- Cited by
- 29
- References
- 16
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 1 · 2019: 6 · 2018: 7
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH106553, R21MH101663)
- National Institute of General Medical Sciences (P20GM103653)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglial activation, lipopolysaccharide, neurodevelopmental disorders, sex differences, interleukin-6, cytokine response, hippocampus, microglia-neuron interaction, autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder, cerebral palsy
- MeSH terms
- Animals, Female, Hippocampus, Lipopolysaccharides, Male, Neuroglia, Neurons, Sex Characteristics, Interleukin-6, Cytokines, Rats, Sprague-Dawley, Microglia, Cell Culture Techniques, Rats, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
