Sex, glia, and development: Interactions in health and disease

Schwarz, Jaclyn M.; Bilbo, Staci D.

doi:10.1016/j.yhbeh.2012.02.018

Cited by 247Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersStress Responses and Cortisol

Sex, glia, and development: Interactions in health and disease

Open access

Schwarz, Jaclyn M., Bilbo, Staci D.·2012·Hormones and Behavior

DOI 10.1016/j.yhbeh.2012.02.018PMC PMC3374064

Open this paper in CoChat — free account

Abstract

Microglia and astrocytes are the primary immune cells within the central nervous system. Microglia influence processes including neural development, synaptic plasticity and cognition; while their activation and production of immune molecules can induce stereotyped sickness behaviors or pathologies including cognitive dysfunction. Given their role in health and disease, we propose that glia may also be a critical link in understanding the etiology of many neuropsychiatric disorders that present with a strong sex-bias in their symptoms or prevalence. Specifically, males are more likely to be diagnosed with disorders that have distinct developmental origins such as autism or schizophrenia. In contrast, females are more likely to be diagnosed with disorders that present later in life, after the onset of adolescence, such as depression and anxiety disorders. In this review we will summarize the evidence suggesting that sex differences in the colonization and function of glia within the normal developing brain may contribute to distinct windows of vulnerability between males and females. We will also highlight the current gaps in our knowledge as well as the future directions and considerations of research aimed at understanding the link between neuroimmune function and sex differences in mental health disorders.

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

Crossref · 10.1016/j.yhbeh.2012.02.018

Cites

137 of 137 references verified0 citation errors · 0 not checkable

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?

Studies in mice show that sex is associated with considerable differences in microglia during and after development.
“Studies in mice have shown that sex is associated with considerable differences in microglia during and after development (53, 54).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [54]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175 · see citing works
Physiology of Microglia
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · see citing works
The Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475 · see citing works
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · see citing works
Tripartite synapses: astrocytes process and control synaptic information
Perea, G., Navarrete, M., & Araque, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.001 · Cited by 1,820 · see citing works
Protoplasmic Astrocytes in CA1 Stratum Radiatum Occupy Separate Anatomical Domains
Bushong, E. A., Martone, M. E., Jones, Y. Z., & Ellisman, M. H. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00183.2002 · Cited by 1,578 · see citing works
Microglial interactions with synapses are modulated by visual experience
Tremblay, M.-È., Lowery, R. L., & Majewska, A. K. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000527 · Cited by 1,542 · see citing works
Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor
Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P., & Vale, W. (1987) · Science · doi:10.1126/science.2821621 · Cited by 1,504 · see citing works
Twenty years of research on cytokine-induced sickness behavior
Dantzer, R., & Kelley, K. W. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.09.006 · Cited by 1,420 · see citing works
Gene–environment interactions in psychiatry: joining forces with neuroscience
Caspi, A., & Moffitt, T. E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1925 · Cited by 1,300 · see citing works
Immune system to brain signaling: Neuropsychopharmacological implications
Capuron, L., & Miller, A. H. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.01.014 · Cited by 1,195 · see citing works
Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1
Berkenbosch, F., van Oers, J., del Rey, A., Tilders, F., & Besedovsky, H. (1987) · Science · doi:10.1126/science.2443979 · Cited by 1,151 · see citing works
Sex hormones and the immune response in humans
Bouman, A., Heineman, M. J., & Faas, M. M. (2005) · Human Reproduction Update · doi:10.1093/humupd/dmi008 · Cited by 1,131 · see citing works
Pubertal hormones organize the adolescent brain and behavior
Sisk, C. L., & Zehr, J. L. (2005) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2005.10.003 · Cited by 1,082 · see citing works
Gene-environment interplay and psychopathology: multiple varieties but real effects
Rutter, M., Moffitt, T. E., & Caspi, A. (2006) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2005.01557.x · Cited by 1,058 · see citing works
Sex Differences in Parasite Infections: Patterns and Processes
Zuk, M., & McKean, K. A. (1996) · International Journal for Parasitology · doi:10.1016/s0020-7519(96)80001-4 · Cited by 993 · see citing works
The Role of Microglia in the Healthy Brain: Figure 1.
Tremblay, M.-È., Stevens, B., Sierra, A., Wake, H., Bessis, A., & Nimmerjahn, A. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4158-11.2011 · Cited by 992 · see citing works
Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain
Perry, V. H., Hume, D. A., & Gordon, S. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90215-5 · Cited by 902 · see citing works
The epidemiology of autoimmune diseases
Cooper, G. S., & Stroehla, B. C. (2003) · Autoimmunity Reviews · doi:10.1016/s1568-9972(03)00006-5 · Cited by 882 · see citing works
Cytokines and CNS Development
Deverman, B. E., & Patterson, P. H. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.002 · Cited by 865 · see citing works
The effects of hormones on sex differences in infection: from genes to behavior
Klein, S. L. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00027-0 · Cited by 839 · see citing works
Regulation of synaptic connectivity by glia.
Eroglu, C., & Barres, B. A. (2010) · Nature · doi:10.1038/nature09612 · Cited by 813 · cited 1× · see citing works
“Astrocytes have an important function in synaptogenesis and synaptic scaling, either through the release of diffusible factors or the production of extracellular matrix proteins [see (Eroglu and Barres, 2010) for review}.”
The X chromosome in immune functions: when a chromosome makes the difference
Libert, C., Dejager, L., & Pinheiro, I. (2010) · Nature reviews. Immunology · doi:10.1038/nri2815 · Cited by 789 · see citing works
Reframing sexual differentiation of the brain
McCarthy, M. M., & Arnold, A. P. (2011) · Nature Neuroscience · doi:10.1038/nn.2834 · Cited by 728 · see citing works
Hormonal and immunological mechanisms mediating sex differences in parasite infection
Klein, S. L. (2004) · Parasite Immunology · doi:10.1111/j.0141-9838.2004.00710.x · Cited by 705 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · 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-citation
Gonadal Steroids and Immunity*
Olsen, N. J., & Kovacs, W. J. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-4-369 · Cited by 659 · see citing works
Early-life programming of later-life brain and behavior: a critical role for the immune system
Bilbo, S. D. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.014.2009 · Cited by 652 · cited 2× · see citing works
“…been done in rodents, which have linked early-life immune challenges to the later-life risk of cognitive disorder with direct implications for glial function in these long-term consequences (Bilbo and Schwarz, 2009; Bilbo and Tsang, 2010; Bilbo, 2010; Bilbo et al., 2011; Williamson et al., 2011).”
Self-citation
DNA Methylation Is a Critical Cell-Intrinsic Determinant of Astrocyte Differentiation in the Fetal Brain
Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M., & Taga, T. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00101-0 · Cited by 608 · see citing works
Effects of gender and sex steroids on the immune response
Schuurs, A. H. W. M., & Verheul, H. A. M. (1990) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(90)90270-3 · Cited by 587 · see citing works
Immune 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
Astrocyte heterogeneity: an underappreciated topic in neurobiology
Zhang, Y., & Barres, B. A. (2010) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.06.005 · Cited by 548 · see citing works
The stem cell potential of glia: lessons from reactive gliosis
Robel, S., Berninger, B., & Götz, M. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn2978 · Cited by 513 · see citing works
Enduring consequences of maternal obesity for brain inflammation and behavior of offspring
Bilbo, S. D., & Tsang, V. (2010) · The FASEB Journal · doi:10.1096/fj.09-144014 · Cited by 489 · see citing works
Self-citation
Specification and Morphogenesis of Astrocytes
Freeman, M. R. (2010) · Science · doi:10.1126/science.1190928 · Cited by 489 · see citing works
Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88‐dependent NFκB signaling, MAPK, and Jak1/Stat1 pathways
Gorina, R., Font-Nieves, M., Márquez‐Kisinousky, L., Santalucı́a, T., & Planas, A. M. (2010) · Glia · doi:10.1002/glia.21094 · Cited by 470 · see citing works
Interleukin-1 is an astroglial growth factor in the developing brain
Giulian, D., Young, D., Woodward, J., Brown, D. M., & Lachman, L. B. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-02-00709.1988 · Cited by 449 · see citing works
Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development
Bushong, E. A., Martone, M. E., & Ellisman, M. H. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2003.12.008 · Cited by 438 · see citing works
Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity
Cutolo, M., Sulli, A., Capellino, S., Villaggio, B., Montagna, P., SERIOLO, B., & Straub, R. H. (2004) · Lupus · doi:10.1191/0961203304lu1094oa · Cited by 407 · see citing works
Principles and Practices of Unbiased Stereology: An Introduction for Bioscientists
Mouton, P. R. (2002) · Cited by 404 · see citing works
The origin and cell lineage of microglia: new concepts
Chan, W. Y., Kohsaka, S., & Rezaie, P. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.11.002 · Cited by 400 · cited 1× · see citing works
“Microglial progenitor cells begin colonizing the rodent brain around embryonic day (E) 9–10 via the infiltration of primitive monocyte precursors from the yolk sac of the embryo (Chan et al., 2007; Ginhoux et al., 2010).”
Genes that escape from X inactivation
Berletch, J. B., Yang, F., Xu, J., Carrel, L., & Disteche, C. M. (2011) · Human Genetics · doi:10.1007/s00439-011-1011-z · Cited by 384 · see citing works
Ultrastructural localization of estrogen receptor β immunoreactivity in the rat hippocampal formation
Milner, T. A., Ayoola, K., Drake, C. T., Herrick, S. P., Tabori, N. E., McEwen, B. S., Mitra, S. W., & Alves, S. E. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20724 · Cited by 358 · see citing works
Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis
Grossman, C. J. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90088-5 · Cited by 341 · see citing works
Induction of PGE2 by estradiol mediates developmental masculinization of sex behavior
Amateau, S. K., & McCarthy, M. M. (2004) · Nature Neuroscience · doi:10.1038/nn1254 · Cited by 340 · see citing works
Cytokine, sickness behavior, and depression
Dantzer, R. (2006) · Neurologic Clinics · doi:10.1016/j.ncl.2006.03.003 · Cited by 340 · see citing works
Interleukins-1 and -6 Stimulate the Release of Corticotropin-Releasing Hormone-41 from Rat Hypothalamusin Vitrovia the Eicosanoid Cyclooxygenase Pathway*
Navarra, P., Tsagarakis, S., Faria, M. D. S., REES, L. H., BESSER, G. M., & Grossman, A. B. (1991) · Endocrinology · doi:10.1210/endo-128-1-37 · Cited by 332 · see citing works
Glial cells in neuronal network function
Araque, A., & Navarrete, M. (2010) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2009.0313 · Cited by 327 · see citing works
The Multifaceted Profile of Activated Microglia
Lynch, M. A. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8077-9 · Cited by 323 · see citing works
A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities
Pace, T. W. W., & Heim, C. M. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.003 · Cited by 321 · 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
Psychoneuroimmunology and the cytokine action in the CNS: Implications for psychiatric disorders
Müller, N., & Ackenheil, M. (1998) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(97)00179-6 · Cited by 304 · see citing works
SEX DIFFERENCES IN SUSCEPTIBILITY TO INFECTIONS
Washburn, T. C., Medearis, D. N., & Childs, B. (1965) · PEDIATRICS · doi:10.1542/peds.35.1.57 · Cited by 299 · see citing works
Altered T cell responses in children with autism
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.09.002 · Cited by 281 · see citing works
Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders
Ashwood, P., Krakowiak, P., Hertz-Picciotto, I., Hansen, R., Pessah, I. N., & Van de Water, J. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.10.025 · Cited by 279 · see citing works
Microglia and Memory: Modulation by Early-Life Infection
Williamson, L. L., Sholar, P. W., Mistry, R. S., Smith, S. H., & Bilbo, S. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3688-11.2011 · Cited by 274 · see citing works
Self-citation
Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology
Abazyan, B., Nomura, J., Kannan, G., Ishizuka, K., Tamashiro, K. L., Nucifora, F., Pogorelov, V., Ladenheim, B., Yang, C., Krasnova, I. N., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.022 · Cited by 255 · see citing works
Glial Fibrillary Acidic Protein: Regulation by Hormones, Cytokines, and Growth Factors
Laping, N. J., Teter, B., Nichols, N. R., Rozovsky, I., & Finch, C. E. (1994) · Brain Pathology · doi:10.1111/j.1750-3639.1994.tb00841.x · Cited by 233 · see citing works
Interactions between Tumor Necrosis Factor-α, Hypothalamic Corticotropin-Releasing Hormone, and Adrenocorticotropin Secretion in the Rat*
BERNARDINI, R., KAMILARIS, T. C., CALOGERO, A. E., JOHNSON, E. O., GOMEZ, M. T., GOLD, P. W., & CHROUSOS, G. P. (1990) · Endocrinology · doi:10.1210/endo-126-6-2876 · Cited by 232 · see citing works
Tripartite synapses: Roles for astrocytic purines in the control of synaptic physiology and behavior
Halassa, M. M., Fellin, T., & Haydon, P. G. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.06.031 · Cited by 229 · see citing works
Estrogen Modulates Microglial Inflammatory Mediator Production via Interactions with Estrogen Receptor β
Baker, A. E., Brautigam, V. M., & Watters, J. J. (2004) · Endocrinology · doi:10.1210/en.2004-0619 · Cited by 227 · see citing works
Gonadal Steroids Promote Glial Differentiation and Alter Neuronal Morphology in the Developing Hypothalamus in a Regionally Specific Manner
Mong, J. A., Glaser, E. M., & McCarthy, M. M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-04-01464.1999 · Cited by 226 · 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
Neonatal Infection Induces Memory Impairments Following an Immune Challenge in Adulthood.
Bilbo, S. D., Levkoff, L. H., Mahoney, J. H., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2005) · Behavioral Neuroscience · doi:10.1037/0735-7044.119.1.293 · Cited by 222 · see citing works
Self-citation
How does the social environment ‘get into the mind’? Epigenetics at the intersection of social and psychiatric epidemiology
Toyokawa, S., Uddin, M., Koenen, K. C., & Galea, S. (2011) · Social Science & Medicine · doi:10.1016/j.socscimed.2011.09.036 · Cited by 219 · see citing works
Microglia and cell death in the developing mouse cerebellum
Ashwell, K. W. S. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90203-b · Cited by 219 · see citing works
Novel roles for immune molecules in neural development: implications for neurodevelopmental disorders
Garay, P. (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00136 · Cited by 217 · see citing works
Female sex steroids: effects upon microglial cell activation
Drew, P. D., & Chavis, J. A. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00386-6 · Cited by 209 · see citing works
A Novel Mechanism of Dendritic Spine Plasticity Involving Estradiol Induction of Prostaglandin-E2
Amateau, S. K., & McCarthy, M. M. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-19-08586.2002 · Cited by 206 · see citing works
Cytokine hypothesis of schizophrenia pathogenesis: Evidence from human studies and animal models
Watanabe, Y., Someya, T., & Nawa, H. (2010) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2010.02094.x · Cited by 204 · see citing works
The distribution of microglia and cell death in the fetal rat forebrain
Ashwell, K. W. S. (1991) · Developmental Brain Research · doi:10.1016/0165-3806(91)90231-7 · Cited by 200 · see citing works
Is autoimmunity a matter of sex?
Lleò, A., Battezzati, P. M., Selmi, C. F., Gershwin, M. E., & Podda, M. (2008) · Autoimmunity Reviews · doi:10.1016/j.autrev.2008.06.009 · Cited by 190 · see citing works
Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide
Santos‐Galindo, M., Acaz‐Fonseca, E., Bellini, M. J., & García‐Segura, L. M. (2011) · Biology of Sex Differences · doi:10.1186/2042-6410-2-7 · Cited by 190 · see citing works
Gender Specific Differences in the Immune Response to Infection
McClelland, E. E., & Smith, J. M. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0124-3 · Cited by 186 · see citing works
Differential Mortality by Sex in Fetal and Neonatal Deaths
McMillen, M. M. (1979) · Science · doi:10.1126/science.571144 · Cited by 181 · see citing works
A role for microglia in synaptic plasticity?
Tremblay, M.-È., & Majewska, A. K. (2011) · Communicative & Integrative Biology · doi:10.4161/cib.4.2.14506 · Cited by 176 · see citing works
Immune dysfunction in autism: A pathway to treatment
Careaga, M., Water, J., & Ashwood, P. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.003 · Cited by 166 · see citing works
Prenatal androgen exposure modulates cellular and humoral immune function of black-headed gull chicks
Müller, W., Groothuis, T. G. G., Kasprzik, A., et al. (2005) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2005.3178 · Cited by 166 · see citing works
Sexual Dimorphism in Autoimmune Disease
McCombe, P., Greer, J. M., & Mackay, I. (2009) · Current Molecular Medicine · doi:10.2174/156652409789839116 · Cited by 166 · see citing works
Sex- and stress-steroids interactions and the immune system: evidence for a neuroendocrine-immunological sexual dimorphism
Gaillard, R. C., & Spinedi, E. (1998) · Domestic Animal Endocrinology · doi:10.1016/s0739-7240(98)00028-9 · Cited by 165 · see citing works
The onset of fever: new insights into its mechanism
Blatteis, C. M. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)62001-3 · Cited by 157 · see citing works
Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation
Swaab, D. F. (2004) · Gynecological Endocrinology · doi:10.1080/09513590400018231 · Cited by 138 · see citing works
Castration alters peripheral immune function in normal male mice.
Viselli, S. M., Stanziale, S. F., Shults, K., Kovacs, W. J., & Olsen, N. J. (1995) · PubMed Central · Cited by 134 · see citing works
A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia
Bilbo, S. D., Smith, S. H., & Schwarz, J. M. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9299-y · Cited by 127 · see citing works
Self-citation
Shield Characteristics Are Testosterone-Dependent in Both Male and Female Moorhens
Eens, M., Duyse, E. V., Berghman, L. R., & Pinxten, R. (2000) · Hormones and Behavior · doi:10.1006/hbeh.1999.1569 · Cited by 125 · see citing works
Role of glial cells in the formation and maintenance of synapses
Pfrieger, F. W. (2010) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.11.002 · Cited by 124 · see citing works
Effects of testosterone and corticosterone on immunocompetence in the zebra finch
Roberts, M. L., Buchanan, K. L., Hasselquist, D., & Evans, M. R. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.09.004 · Cited by 124 · see citing works
Helminth growth in vertebrate hosts: Does host sex matter?
Poulin, R. (1996) · International Journal for Parasitology · doi:10.1016/s0020-7519(96)00108-7 · Cited by 121 · see citing works
An Ounce of Prevention Is a Ton of Work: Mass Antibiotic Prophylaxis for Anthrax, New York City, 2001
Blank, S., Moskin, L. C., & Zucker, J. R. (2003) · Emerging infectious diseases · doi:10.3201/eid0906.030118 · Cited by 114 · see citing works
Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline
Bilbo, S. D. (2010) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2010.04.001 · Cited by 108 · see citing works
Self-citation
Macrophages in Alzheimer’s disease: the blood-borne identity
Gate, D., Rezai-Zadeh, K., Jodry, D., Rentsendorj, A., & Town, T. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0422-7 · Cited by 107 · see citing works
A behavioural characterization of neonatal infection-facilitated memory impairment in adult rats
Bilbo, S. D., Rudy, J. W., Watkins, L. R., & Maier, S. F. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.12.002 · Cited by 106 · see citing works
Self-citation
Early-life infection leads to altered BDNF and IL-1β mRNA expression in rat hippocampus following learning in adulthood
Bilbo, S. D., Barrientos, R. M., Eads, A. S., Northcutt, A. L., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.10.003 · Cited by 104 · see citing works
Self-citation
Early maternal deprivation in rats induces gender‐dependent effects on developing hippocampal and cerebellar cells
Llorente, R., López‐Gallardo, M., Llorente‐Berzal, A., Prada, C., García‐Segura, L. M., & Viveros, M. (2009) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2009.01.002 · Cited by 101 · see citing works
Evidence for Sexual Differentiation of Glia in Rat Brain
Mong, J. A., Kurzweil, R. L., Davis, A. M., Rocca, M. S., & McCarthy, M. M. (1996) · Hormones and Behavior · doi:10.1006/hbeh.1996.0058 · Cited by 96 · see citing works
Estrogen regulation of immune responses after injury
Kovacs, E. J., Messingham, K. N., & Gregory, M. S. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00106-5 · Cited by 96 · see citing works
Prostaglandin E2-Induced Masculinization of Brain and Behavior Requires Protein Kinase A, AMPA/Kainate, and Metabotropic Glutamate Receptor Signaling
Wright, C. L., & McCarthy, M. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3603-09.2009 · Cited by 90 · see citing works
Brain microglia express steroid-converting enzymes in the mouse
Gottfried‐Blackmore, A., Sierra, A., Jellinck, P. H., McEwen, B. S., & Bulloch, K. (2008) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2007.12.013 · Cited by 90 · see citing works
Inflammation and gliosis in neurological diseases – clinical implications
Członkowska, A., & Kurkowska‐Jastrzębska, I. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.09.020 · Cited by 89 · see citing works
Local and humoral immune responses against primary and repeat Neisseria gonorrhoeae genital tract infections of 17β-estradiol-treated mice
Song, W., Condron, S., Mocca, B. T., et al. (2008) · Vaccine · doi:10.1016/j.vaccine.2008.08.020 · Cited by 87 · see citing works
A Multivariate Twin Study of Autistic Traits in 12-Year-Olds: Testing the Fractionable Autism Triad Hypothesis
Robinson, E., Koenen, K. C., McCormick, M. C., Münir, K., Hallett, V., Happe, F. G. E., Plomin, R. J., & Ronald, A. (2011) · Behavior Genetics · doi:10.1007/s10519-011-9500-3 · Cited by 85 · see citing works
Oestrogen and Progesterone Reduce Lipopolysaccharide‐Induced Expression of Tumour Necrosis Factor‐α and Interleukin‐18 in Midbrain Astrocytes
Kipp, M., Karakaya, S., Johann, S., Kampmann, E., Mey, J., & Beyer, C. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01588.x · Cited by 83 · see citing works
Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.
Amstadter, A. B., Nugent, N. R., Yang, B., Miller, A. B., Siburian, R., Moorjani, P., Haddad, S. A., Basu, A., Fagerness, J. A., Saxe, G., et al. (2011) · Europe PMC (PubMed Central) · doi:10.3233/dma-2011-0761 · Cited by 83 · see citing works
A novel model for prenatal brain damage
Nuñez, J. L., Alt, J., & McCarthy, M. M. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00051-7 · Cited by 75 · see citing works
LPS elicits a much larger and broader inflammatory response than Escherichia coli infection within the hippocampus of neonatal rats
Schwarz, J. M., & Bilbo, S. D. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.04.042 · Cited by 74 · see citing works
Self-citation
Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients
Amstadter, A. B., Nugent, N. R., Yang, B., Miller, A. B., Siburian, R., Moorjani, P., Haddad, S. A., Basu, A., Fagerness, J. A., Saxe, G., et al. (2011) · Disease Markers · doi:10.1155/2011/928497 · Cited by 72 · see citing works
Chapter 1 Normal Brain Aging
Caserta, M. T., Bannon, Y., Fernandez, F., Giunta, B. N., Schoenberg, M. R., & Tan, J. (2009) · International review of neurobiology · doi:10.1016/s0074-7742(09)00401-2 · Cited by 70 · see citing works
Identification of prostaglandin E2 receptors mediating perinatal masculinization of adult sex behavior and neuroanatomical correlates
Wright, C. L., Burks, S. R., & McCarthy, M. M. (2008) · Developmental Neurobiology · doi:10.1002/dneu.20665 · Cited by 69 · see citing works
Microglia in the human fetal spinal cord—patterns of distribution, morphology and phenotype
Rezaie, P., Patel, K., & Male, D. K. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00043-7 · Cited by 68 · see citing works
The X in sex: how autoimmune diseases revolve around sex chromosomes
Selmi, C. F. (2008) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2008.09.002 · Cited by 64 · see citing works
Effect of estrogen on natural killer cells
Seaman, W. E., & Gindhart, T. D. (1979) · Arthritis & Rheumatism · doi:10.1002/art.1780221110 · Cited by 59 · see citing works
Effects of Sex Hormones on Some T and B Cell Functions, Evidenced by Differential Immune Expression Between Male and Female Mice and Cyclic Pattern of Immune Responsiveness During the Estrous Cycle in Female Mice*
Krzych, U., Strausser, H. R., Bressler, J. P., et al. (1981) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.1981.tb00020.x · Cited by 57 · see citing works
Sex differences in response to kainic acid and estradiol in the hippocampus of newborn rats
Hilton, G. D., Nu�ez, J. L., & McCarthy, M. M. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00716-9 · Cited by 56 · see citing works
Neonatal lipopolysaccharide exposure impairs sexual development and reproductive success in the Wistar rat
Walker, A. K., Hiles, S. A., Sominsky, L., McLaughlin, E. A., & Hodgson, D. M. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.01.004 · Cited by 54 · see citing works
Is testosterone immunosuppressive in a condition-dependent manner? An experimental test in blue tits
Roberts, M., & Peters, A. (2009) · Journal of Experimental Biology · doi:10.1242/jeb.031047 · Cited by 50 · see citing works
Neuron–glia signaling: Implications for astrocyte differentiation and synapse formation
Stipursky, J., Romão, L. F., Tortelli, V., Moura‐Neto, V., & Gomes, F. C. A. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.04.005 · Cited by 47 · see citing works
Influence of gender and age on T-cell responses in a murine model of trauma-hemorrhage: differences between circulating and tissue-fixed cells
Schneider, C. P., Schwacha, M. G., & Chaudry, I. H. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00898.2005 · Cited by 41 · see citing works
Variation with age in the labelling of amoeboid microglial cells in rats following intraperitoneal or intravenous injection of a fluorescent dye.
Xu, J., Kaur, C., & Ling, E. A. (1993) · PubMed · Cited by 40 · see citing works
Minireview: Early-Life Programming by Inflammation of the Neuroendocrine System
Kentner, A. C., & Pittman, Q. J. (2010) · Endocrinology · doi:10.1210/en.2010-0583 · Cited by 37 · see citing works
Estradiol Modulation of Astrocytes and the Establishment of Sex Differences in the Brain
McCarthy, M. M., Todd, B. J., & Amateau, S. K. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1286.027 · Cited by 32 · see citing works
Sex Hormones and the Immune Response
Feigen, G. A., Fraser, R. C., & Peterson, N. S. (2009) · International Archives of Allergy and Applied Immunology · doi:10.1159/000232143 · Cited by 32 · see citing works
Potentiation of tumor metastasis in adulthood by neonatal endotoxin exposure: sex differences
Hodgson, D. M., & Knott, B. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00080-4 · Cited by 28 · see citing works
Microglia express functional 11β‐hydroxysteroid dehydrogenase type 1
Gottfried‐Blackmore, A., Sierra, A., Mcewen, B. S., Ge, R., & Bulloch, K. (2010) · Glia · doi:10.1002/glia.21007 · Cited by 27 · see citing works
Colonisation of the human central nervous system by microglia: the roles of chemokines and vascular adhesion molecules
Male, D. K., & Rezaie, P. (2001) · Progress in brain research · doi:10.1016/s0079-6123(01)32067-8 · Cited by 26 · see citing works
Can we explain the higher prevalence of autoimmune disease in women?
Kivity, S., & Ehrenfeld, M. (2010) · Expert Review of Clinical Immunology · doi:10.1586/eci.10.60 · Cited by 26 · see citing works
Sex Steroid Regulation of Microglial Cell Activation: Relevance to Multiple Sclerosis
DREW, P. D., CHAVIS, J. A., & BHATT, R. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1286.031 · Cited by 25 · see citing works
Microglial distribution and apoptosis in fetal rat brain
Wang, C.-C., Wu, C., Shieh, J.-Y., & Wen, C.-Y. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(02)00584-9 · Cited by 23 · see citing works
ErbB receptor signaling in astrocytes: A mediator of neuron-glia communication in the mature central nervous system
Sharif, A., & Prévot, V. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.05.012 · Cited by 22 · see citing works
The Impact of Hormone Replacement Therapy on Humoral and Cell‐mediated Immune Responses In Vivo in Post‐menopausal Women with Rheumatoid Arthritis
Forsblad‐d’Elia, H., & Carlsten, H. (2008) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2008.02186.x · Cited by 21 · see citing works
Androgenic Effects on Hypothalamic Asymmetry in a Sexually Differentiated Nucleus Related to Vocal Behavior in Mongolian Gerbils
Holman, S. D., & Rice, A. (1996) · Hormones and Behavior · doi:10.1006/hbeh.1996.0067 · Cited by 13 · see citing works
The Relationship of X-Linked Primary Immune Deficiencies and Autoimmunity
Pessach, I. M. (2010) · Current Allergy and Asthma Reports · doi:10.1007/s11882-010-0127-x · Cited by 12 · see citing works
Co-culture with microglia promotes neural stem cells differentiation into astrocytes.
Gu, F., Wang, J., Fu, L., et al. (2011) · PubMed · Cited by 11 · see citing works
Propiedades neuroprotectoras de los esteroides sexuales y los neuroesteroides
Veiga, S. J., García‐Segura, L. M., & Azcoitia, Í. (2004) · Revista de Neurología · doi:10.33588/rn.3911.2004555 · Cited by 10 · see citing works
Neuronal Cell Death During Sexual Differentiation and Lateralisation of Vocal Communication
Holman, S. D. (1998) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(98)00001-3 · Cited by 8 · see citing works
Postnatal cell proliferation and death in a lateralized, gender‐related, asymmetric nucleus
Holman, S. D., & Collado, P. (2001) · Journal of Neurobiology · doi:10.1002/neu.1022 · Cited by 4 · see citing works
Immune Dysfunction in Autism
Marazziti, D. (2003) · CRC Press eBooks · doi:10.3109/9780203911723-12 · Cited by 3 · see citing works

Flagged first, then by citations

Sorted by citations

Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894 · see citing works
Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species
Semple, B. D., Blomgren, K., Gimlin, K., Ferriero, D. M., & Noble-Haeusslein, L. J. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.001 · Cited by 2,132 · see citing works
Sex differences in autism spectrum disorders
Werling, D. M., & Geschwind, D. H. (2013) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32835ee548 · Cited by 1,245 · see citing works
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934 · see citing works
Transcriptional and Translational Differences of Microglia from Male and Female Brains
Guneykaya, D., Ivanov, A., Hernandez, D. P., Haage, V., Wojtas, B., Meyer, N., Maricos, M., Jordan, P., Buonfiglioli, A., Gielniewski, B., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.08.001 · Cited by 477 · see citing works
Estrogens, Neuroinflammation, and Neurodegeneration
Villa, A., Vegeto, E., Poletti, A., & Maggi, A. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1007 · Cited by 423 · see citing works
Microglia Function in Central Nervous System Development and Plasticity
Schafer, D. P., & Stevens, B. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020545 · Cited by 353 · see citing works
Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation
Elmore, M. R. P., Lee, R. J., West, B. L., & Green, K. N. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122912 · Cited by 228 · see citing works
NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: A bipartisan affair?
Bordt, E. A., & Polster, B. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.033 · Cited by 202 · see citing works
Effects of Microglia on Neurogenesis
Sato, K. (2015) · Glia · doi:10.1002/glia.22858 · Cited by 187 · see citing works
Sex differences in microglia activity within the periaqueductal gray of the rat: A potential mechanism driving the dimorphic effects of morphine
Doyle, H. H., Eidson, L. N., Sinkiewicz, D. M., & Murphy, A. Z. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2906-16.2017 · Cited by 166 · see citing works
Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development
Reynolds, L. M., & Flores, C. (2021) · Frontiers in Neural Circuits · doi:10.3389/fncir.2021.735625 · Cited by 137 · see citing works
Bridging autism spectrum disorders and schizophrenia through inflammation and biomarkers – pre-clinical and clinical investigations
Prata, J., Santos, S. G., Almeida, M. I., Coelho, R., & Barbosa, M. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0938-y · Cited by 115 · see citing works
Neonatal lipopolysaccharide exposure induces long-lasting learning impairment, less anxiety-like response and hippocampal injury in adult rats
Wang, K.-C., Fan, L.-W., Kaizaki, A., Pang, Y., Cai, Z., & Tien, L.-T. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.049 · Cited by 92 · see citing works
Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse
Klocke, C., Allen, J. L., Sobolewski, M., Mayer-Pröschel, M., Blum, J. L., Lauterstein, D., Zelikoff, J. T., & Cory-Slechta, D. A. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx010 · Cited by 87 · see citing works
Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study
Hegvik, T.-A., Instanes, J. T., Haavik, J., Klungsøyr, K., & Engeland, A. (2018) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-017-1056-1 · Cited by 79 · see citing works
Sex differences in prefrontal cortex microglia morphology: Impact of a two-hit model of adversity throughout development
Gildawie, K. R., Orso, R., Peterzell, S., Thompson, V., & Brenhouse, H. C. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135381 · Cited by 46 · see citing works
Enhanced cerebellar myelination with concomitant iron elevation and ultrastructural irregularities following prenatal exposure to ambient particulate matter in the mouse
Klocke, C., Sherina, V., Graham, U. M., Gunderson, J., Allen, J. L., Sobolewski, M., Blum, J. L., Zelikoff, J. T., & Cory-Slechta, D. A. (2018) · Inhalation Toxicology · doi:10.1080/08958378.2018.1533053 · Cited by 41 · see citing works

Contributions of Microglia in the Healthy and Injured Brain
Rice, R. A. (2015) · eScholarship (California Digital Library)
Microglia in multiple sclerosis: protectors turn destroyers
Yong, V. W. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.023 · Cited by 185 · see citing works
Microglia derived from the axotomized adult rat facial nucleus uptake glutamate and metabolize it to glutamine in vitro
Nakajima, K., Kanamatsu, T., Koshimoto, M., & Kohsaka, S. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.10.015 · Cited by 7 · see citing works
Iron loading is a prominent feature of activated microglia in Alzheimer’s disease patients
Kenkhuis, B., Somarakis, A., de Haan, L., Dzyubachyk, O., IJsselsteijn, M. E., de Miranda, N. F. C. C., Lelieveldt, B. P. F., Dijkstra, J., van Roon-Mom, W. M. C., Höllt, T., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01126-5 · Cited by 184 · see citing works
Microglial Kv1.3 Channels as a Potential Target for Alzheimer's Disease
Jenkins, D. P., Maezawa, I., Wulff, H., et al. (2012) · The FASEB Journal · doi:10.1096/fasebj.26.1_supplement.695.16 · Cited by 1 · see citing works

Authors: Schwarz, J. M., & Bilbo, S. D.
Affiliations: Duke University (US)
Corresponding author: Schwarz, Jaclyn M.
ORCID: Schwarz, Jaclyn M.
Bilbo, Staci D.
Venue: Hormones and Behavior
Publisher: Elsevier BV
Published: 2012-08
Volume: 62
Issue: 3
Pages: 243-253
ISSN: 0018-506X (ISSN-L)
DOI: 10.1016/j.yhbeh.2012.02.018
PMC: PMC3374064
OpenAlex: W2048380200
Cited by: 247
References: 137
Citations by year: 2026: 14 · 2025: 9 · 2024: 8 · 2023: 16 · 2022: 10 · 2021: 27 · 2020: 15 · 2019: 28 · 2018: 28 · 2017: 24 · 2016: 14 · 2015: 20 · 2014: 16 · 2013: 13 · 2012: 4
FWCI: 1.58
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Hormones and Behavior (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (R01DA025978, F32DA030136)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: sex differences, microglia, astrocytes, glia, neuroimmune function, neuropsychiatric disorders, brain development, autism spectrum disorder, schizophrenia, depression, anxiety disorders, sickness behavior, cognitive impairment, window of vulnerability
MeSH terms: Animals, Mental Disorders, Brain, Female, Male, Neuroglia, Sex Characteristics

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

Sex, glia, and development: Interactions in health and disease

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks