The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition
Open accessAbstract
We have reported that neonatal infection leads to memory impairment after an immune challenge in adulthood. Here we explored whether events occurring as a result of early infection alter the response to a subsequent immune challenge in adult rats, which may then impair memory. In experiment 1, peripheral infection with Escherichia coli on postnatal day 4 increased cytokines and corticosterone in the periphery, and cytokine and microglial cell marker gene expression in the hippocampus of neonate pups. Next, rats treated neonatally with E. coli or PBS were injected in adulthood with lipopolysaccharide (LPS) or saline and killed 1-24 h later. Microglial cell marker mRNA was elevated in hippocampus in saline controls infected as neonates. Furthermore, LPS induced a greater increase in glial cell marker mRNA in hippocampus of neonatally infected rats, and this increase remained elevated at 24 h versus controls. After LPS, neonatally infected rats exhibited faster increases in interleukin-1beta (IL-1beta) within the hippocampus and cortex and a prolonged response within the cortex. There were no group differences in peripheral cytokines or corticosterone. In experiment 2, rats treated neonatally with E. coli or PBS received as adults either saline or a centrally administered caspase-1 inhibitor, which specifically prevents the synthesis of IL-1beta, 1 h before a learning event and subsequent LPS challenge. Caspase-1 inhibition completely prevented LPS-induced memory impairment in neonatally infected rats. These data implicate IL-1beta in the set of immune/inflammatory events that occur in the brain as a result of neonatal infection, which likely contribute to cognitive alterations in adulthood.
Overview
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
Verification
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?
In the citing paper
“Bilbo et al. revealed that neonatal E. coli infection could impair memory in adult rats (394).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [394]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · cited 1×
“To adjust for variability in tissue sample sizes, total protein concentrations were determined by Coomassie Brilliant Blue AG-250 protein assay (Bradford, 1976).”
MethodAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · cited 1×
“Relative gene expression was determined using the 2 -⌬⌬Ct method (Livak and Schmittgen, 2001; Pfaffl, 2001).”
MethodSingle-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515 · cited 1×
“Total RNA was isolated from hippocampal tissue based on the TRIzol method of Chomczynski and Sacchi (1987) and has been described in detail previously (Frank et al., 2005).”
MethodA new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · cited 2×
“Relative gene expression was determined using the 2 -⌬⌬Ct method (Livak and Schmittgen, 2001; Pfaffl, 2001).”
MethodMutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Comparative aspects of the brain growth spurt
Dobbing, J., & Sands, J. (1979) · Early Human Development · doi:10.1016/0378-3782(79)90022-7 · Cited by 2,506 · cited 2×
“, 2001) and represents a time relatively comparable with the third trimester in humans during which significant brain growth occurs (Dobbing and Sands, 1979; Rodier, 1980).”
BackgroundMethodBrain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777 · cited 1×
“Role of IL-1 in memory impairment Patients with acquired immunodeficiency syndrome (AIDS)related dementia, cancer, or chronic inflammatory diseases often exhibit elevated levels of IL-1 co-occurring with cognitive impairment (Gallo et al., 1989; Griffin et al., 1989; Stanley et al., 1994; Meyers, 2000).”
BackgroundMaier, S. F., & Watkins, L. R. (1998) · Psychological Review · doi:10.1037/0033-295x.105.1.83 · Cited by 1,130 · cited 1×
“IL-1 is the most consistently induced cytokine in the brain after peripheral immune stimulation and has a high density of receptors in the hippocampus (Maier and Watkins, 1998).”
BackgroundSelf-citationMicroglia and neuroinflammation: a pathological perspective
Streit (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-14 · Cited by 1,039
Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring
Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00297.2003 · Cited by 1,025 · cited 3×
“Furthermore, an increasing body of evidence from both animal (Hornig et al., 1999; Shi et al., 2003) and human (Rantakallio et al.”
Background
Research works printed but not linked: 8
- 1995, Conference report: fetal origins of adult disease—report of the First International Study Group, 16, 317
- 1997, Chem Immunol, 69, 31
- 10.1016/0003-2697(87)90021-2 · DOI
- 2004, Clin Diagn Lab Immunol, 11, 621
- 2000, Oncology, 14, 75
- 1998, Endocr Regul, 32, 77
- 2000, Neuroscience, 95, 577
- 1994, Q J Exp Psychol B, 47, 427
Cited by
Sorted by citations
Items 201–250 of 250
Özgöçer, T., Yıldız, S., Elbe, H., & Vardı, N. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2014-0559 · Cited by 6
Gomez, J., Haas, N. A., & Schwarz, J. M. (2019) · Psychopharmacology · doi:10.1007/s00213-019-05194-3 · Cited by 6
Understanding Barrier Mechanisms In the Developing Brain To Aid Therapy For the Dysfunctional Brain
Saunders, N. R., & Habgood, M. D. (2011) · Future Neurology · doi:10.2217/fnl.10.84 · Cited by 6
Khatib, N., Weiner, Z., Ginsberg, Y., Awad, N., & Beloosesky, R. (2017) · Rambam Maimonides Medical Journal · doi:10.5041/rmmj.10303 · Cited by 6
Gomes, C. I., & Barr, G. A. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100175 · Cited by 5
“This protocol was adapted from the work of Bilbo and Schwarz (Bilbo et al., 2005a, 2008; Bilbo and Schwarz, 2012).”
InfluentialSickness-induced changes in physiology do not affect fecundity or same-sex behavior
Sylvia, K. E., Ramos, P. B., & Demas, G. E. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.11.002 · Cited by 5
Early life inflammation — it sticks to the brain
Pittman, Q., Gomez, C. D., Read, J., Lewis, M. L., & Acharjee, S. (2019) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2019.02.008 · Cited by 4
Shaw, C. A. (2017) · Wiley eBooks · doi:10.1002/9781118634523.refs · Cited by 9
Orr, A. G., Sharma, A. K., Binder, N. B., Miller, A. H., & Pearce, B. D. (2009) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9293-5 · Cited by 4
“…is growing evidence that induction of IL-1 may represent a common pathway by which both infectious and noninfectious (e.g., hypoxia) insults can cause neurodevelopmental abnormalities of the hippocampus that result in long-term sequela (Szaflarski et al. 1995; Bilbo et al. 2005; Hu et al. 2005).”
BackgroundIs programming of weight regulation immune to neonatal inflammation?
Luheshi, G. N., & Rummel, C. D. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00376.2007 · Cited by 4
“Previous reports have implicated long-term changes in the levels of proinflammatory cytokines, including TNF- and IL-1 , the changes in the concentration of which were associated with alterations of various physiological parameters following LPS treatment of neonates (4, 10, 29).”
BackgroundSharma, R., Kearns, M. M., Sarr, F., & Ismail, N. (2019) · Immunology Letters · doi:10.1016/j.imlet.2019.03.005 · Cited by 4
Caesarine, A., Batorsky, R., Shook, L. L., Kışlal, S., Bordt, E. A., Devlin, B. A., Perlis, R. H., Slonim, D. K., Bilbo, S. D., & Edlow, A. G. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3985607 · Cited by 4
Helmbrecht, H., Ardalan, M., Kelly, L. A., Robinson, S., Fleiss, B., Doherty, D. G., Gressèns, P., Mallard, C. E., Molloy, E. J., & Jantzie, L. L. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03900-5 · Cited by 3
“Immune plasticity altered by in-utero insults may have long-term effects on the inflammatory responses of circulating leukocytes, which could serve as a biomarker of persistent or prior neuroinflammation and brain injury [248, 249].”
Neuro-immune interactions in memory
Stewart, E., & Ryan, T. J. (2025) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2025.108077 · Cited by 3
Symptom research: looking ahead
Cleeland, C. S., Fisch, M. J., & Dunn, A. J. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511780868.034 · Cited by 2
Fanikos, M., Kohn, S. A., Stamato, R., Brenhouse, H. C., & Gildawie, K. R. (2024) · PLoS ONE · doi:10.1371/journal.pone.0306022 · Cited by 3
Accelerated maturation of fear regulation systems in infant rats following early life inflammation
McCutcheon, T. B., Simenson-Braun, S. M., & Richardson, R. (2025) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2025.108109 · Cited by 1
Neonatal lipopolysaccharide administration causes long-term changes in mouse immunosteroids
Salehzadeh, M., Mazurenko, A., & Soma, K. K. (2026) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00135.2025 · Cited by 1
Burrowes, K. A., Nikodémová, M., & Mitchell, G. S. (2026) · Function · doi:10.1152/function.074.2025 · Cited by 1
Bajaj, H., Salehzadeh, M., Mazurenko, A., Choo, C., Ciernia, A., & Soma, K. K. (2026) · Hormones and Behavior · doi:10.1016/j.yhbeh.2026.105888 · Cited by 1
Miyauchi, O., Iwase, K., Itoh, K., Kato, M., Seki, N., Braissant, O., Bachmann, C., Shozu, M., Sekiya, S., Osada, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079236 · Cited by 1
“For example, LPS and IFNc are thought to be involved in brain disorders [4–6] such as those arising from perinatal intrauterine infections that cause various brain injuries ranging from periventricular leukomalacia (PVL) with permanent motor impairment [4,7] to adult-onset neuropsychiatric disorders [8,9].”
BackgroundEpigenetics and Late-Onset Alzheimer’s Disease
Schumacher, A., Bihaqi, S. W., & Zawia, N. H. (2011) · Springer eBooks · doi:10.1007/978-1-84882-644-1_12 · Cited by 1
General Characteristics of Human Neonate Immunity
Qi, Z., Mou, W., He, J., & Gui, J. (2014) · American Journal of Biomedical Sciences · doi:10.5099/aj140400265 · Cited by 1
“characterized by an absence of memory T cells and a slow adaptive immune response with tolerance features [25].”
BackgroundNeonatal Proinflammatory Stress and the Maturation of Intercellular Communication in the Hippocampus
Kudryashova, I. V., Stepanichev, M. Y., & Gulyaeva, N. V. (2020) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-020-00971-6 · Cited by 1
“…ammatory stress does not lead to any notable changes in the baseline IL-1β and TNF-α contents in the brains of young animals in the state of rest [Bilbo et al., 2005; Onufriev et al., 2017], though increases in IL-1β in response to the corresponding signals were signifi cantly greater in such…”
BackgroundMethodInfluentialMicroglia and Neurodevelopment: Programming of Cognition throughout the Lifespan
Schwarz, J. M., & Bilbo, S. D. (2013) · doi:10.1002/9781118314814.ch15 · Cited by 1
Dziabis, J. E., Jonathan, I. O., Horvath, B. L., Zhang, G., Patton, M. S., Smith, C. J. W., Nguyen, D. M., Jammula, M., Devlin, B. A., Monroe, S. K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.08.692987 · Cited by 1
“The timing and dose of injection was selected based on previous work from the lab (Bilbo et al., 2005b, 2005a; Bland et al., 2010; Schwarz and Bilbo, 2011; Smith et al., 2020; Williamson et al., 2011) Microglia 2-”
Bolton, J. L. (2015) · DukeSpace (Duke University)
Neuroimmune Signaling in the Hippocampus: Mechanisms of Risk and Resilience
Williamson, L. L. (2014) · DukeSpace (Duke University)
Neonatal Experimental White Matter Injury
Cai, Z. (2013) · Springer eBooks · doi:10.1007/978-1-4614-9123-1_7
Predicting Health: The Role of the Early‐Life Environment
Sominsky, L., Walker, A. K., & Hodgson, D. M. (2013) · Wiley eBooks · doi:10.1002/9781118314814.ch14
Hosseini, M., Soukhtanloo, M., Zabihi, H., & Hadjzadeh, M. A.-R. (2014)
Fever and sickness behaviour during simulated Mycoplasma infection in rats
Swanepoel, T. (2013) · University of the Witwatersrand, Johannesburg Institutional Repository on DSpace (University of the Witwatersrand, Johannesburg)
Topper, L. A. (2015) · UNM’s Digital Repository (University of New Mexico)
Influência do LPS e do zinco na interação mãe e filhote
do Nascimento, A. F. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2016.tde-04052016-152636
Magni, D. V. (2011) · Americanae (AECID Library)
Maryam, M.-Z., Hanieh, A., Mohsen, S., Ali-Akbar, E., & Salari (2013)
Early Life Events With Microbiota Mediated Effects on Brain Functions
Ignjatović, Đ. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00058-9
Maier, S. F., & Watkins, L. R. (2009) · Wiley eBooks · doi:10.1002/9780470478509.neubb001008
Mulkey, D. K. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735376690.793566072
Maurer, S. V., Bolton, J. L., Bilbo, S. D., & Williams, C. L. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.04.522511
Postnatal Development of Neuroimmune Responses
Spencer, S. J. (2023) · Masterclass in neuroendocrinology · doi:10.1007/978-3-031-21358-8_9
Rong, J., Yang, Y., Liang, M., Zhong, H., Li, Y., Zhu, Y., Sha, S., Chen, L., & Zhou, R. (2024) · Figshare · doi:10.6084/m9.figshare.26563561
Singh, G., Segura, B. J., Georgieff, M. K., & Gisslen, T. A. (2021) · Figshare · doi:10.6084/m9.figshare.14205459
Minocycline differentially modulates human spatial memory systemsPreprint
Bird, C. M., Harrison, N. A., & Berens, S. C. (2020) · OSF Preprints (OSF Preprints)
Dorman, T. A., & Boschen, K. E. (2026) · Physiology & Behavior · doi:10.1016/j.physbeh.2026.115377
Context-dependent effects of microglial MyD88 removal on voluntary ethanol consumption in mice
Dziabis, J. E., Rogers, N., Horvath, B. L., Patton, M. S., Jonathan, I. O., Freeman, E. J., Sun, W., Moulden, J., Zhang, G., & Bilbo, S. D. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111076
Before the insult: Why the microglial starting state matters in neurodegeneration
Szelechowski, M. (2026) · Glial health research. · doi:10.1016/j.ghres.2026.100022
Shirokov, E., Nikitina, V., Kim, E., & Trofimov, A. (2026) · Research Square · doi:10.21203/rs.3.rs-11152567/v1
Metadata
- Authors
- Bilbo, S. D., Biedenkapp, J. C., Der-Avakian, A., Watkins, L. R., Rudy, J. W., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-08-31
- Volume
- 25
- Issue
- 35
- Pages
- 8000-8009
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725459
- OpenAlex
- W2042311033
- Cited by
- 251
- References
- 71
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 9 · 2023: 9 · 2022: 6 · 2021: 18 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 28 · 2016: 9 · 2015: 17 · 2014: 20 · 2013: 24 · 2012: 12
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH065656, R01-MH065656-02)
- 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
- neonatal infection, lipopolysaccharide, memory impairment, caspase-1 inhibition, IL-1β, hippocampus, microglia, neuroinflammation, Escherichia coli, corticosterone, cytokines, learning, neuroimmune interactions
- MeSH terms
- Age Factors, Animals, Animals, Newborn, Enzyme Inhibitors, Escherichia coli Infections, Female, Hippocampus, Interleukin-1, Lipopolysaccharides, Male, Memory Disorders, Pregnancy, Rats, Sprague-Dawley, Caspase 1, Rats, Caspase Inhibitors
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
