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Regulation of the Gene Encoding Tumor Necrosis Factor Alpha (TNF-α) in the Rat Brain and Pituitary in Response to Different Models of Systemic Immune Challenge
Abstract
Tumor necrosis factor (TNF)-alpha is usually referred to as a proinflammatory cytokine that plays a central role in initiating the cascade of other cytokines and factors for an appropriate immune response to infection. Like systemic phagocytes, recent studies have reported that specific cellular populations of the CNS have the ability to express and release the proinflammatory cytokine in response to peripheral administration of the bacterial endotoxin lipopolysaccharide (LPS). Whether such phenomenon represents a general mechanism of systemic immunogenic stimuli and how the severity of the challenge may influence TNF-alpha transcription in the brain has yet to be defined. Adult male rats were sacrificed 1, 3, 6, 12, 24 and 48 hours (h) after intraperitoneal (IP) injection of LPS (25-250 microg/100 g) or intramuscular (IM) injection of turpentine. Brains and pituitary glands were removed, cut, and TNF-alpha mRNA assayed by in situ hybridization using a full-length rat cRNA probe. The results show no positive signal under basal conditions or following sterile inflammation into the left hind limb. Systemic LPS caused a profound increase in the expression of the gene encoding TNF-alpha in the leptomeninges, choroid plexus (chp) and all sensorial circumventricular organs (CVOs). Interestingly, a migratory-like pattern of TNF-alpha-positive cells became apparent around the sensorial CVOs at 3 h, while a ubiquitous-like positive signal was found throughout the brain 6 h after the injection with the highest dose of LPS. The IP LPS injection also stimulated TNF-alpha transcription in the anterior pituitary lobe; the signal was maximal 1 h after the injection and returned gradually to basal levels at 12 h, whereas the mRNA encoding the cytokine was detected later in the neurohypophysis, i.e. 3 and 6 h post challenge. Dual-labeling procedure provided the evidence of an LPS-dependent induction of TNF-alpha in different phagocytic cellular populations of the brain, including parenchymal microglial cells during severe endotoxemia. The fact that these myeloid-derived cells have the ability to express the LPS receptor CD14 in the brain may well explain the transcriptional activation of the cytokine in response to the bacterial endotoxin, but not to systemic localized inflammation.
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“LPS administration is also known to promote rapid expression of pro-inflammatory cytokines such as TNFα in all sensory CVOs as well as the meninges and choroid plexus (102).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [102]
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“However, asmentioned before, it has also been demonstrated that these cytokines can be generated in the central nervous system, particularly in the hypothalamus and nearby areas after LPS or Poly I:C injection (Vallieres and Rivest, 1997; Nadeau and Rivest, 1999; Katafuchi et al., 2005; Cunningham et al., 2007; Konat…”
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“cell dysfunction [78], inducing the rupture of the BBB.”
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Kawai, S., Kurganov, E., & Miyata, S. (2020) · Cell Biochemistry and Function · doi:10.1002/cbf.3477 · Cited by 8
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Pavlov, V. A., Ulloa, L., & Metz, C. N. (2010) · Neuroimmune biology · doi:10.1016/s1567-7443(10)70027-2 · Cited by 7
Differential expression of class I MHC mRNA in the hypothalamus of Lewis and Fischer rats
Puchowicz, M. J., Tonelli, L. H., & Sternberg, E. M. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00421-6 · Cited by 5
Jada, R., Zag, L., Borisov, V., Levy, N. S., Netser, S., Jabarin, R., Wagner, S., Rozales, K., Shalgi, R., & Levy, A. P. (2021) · International Journal of Hyperthermia · doi:10.1080/02656736.2021.1988730 · Cited by 4
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Emanuele, N., LaPaglia, N., Kovacs, E. J., Gamelli, R. L., & Emanuele, M. A. (2008) · Journal of Burn Care & Research · doi:10.1097/bcr.0b013e3181711273 · Cited by 4
Proinflammatory signal transduction pathways in the CNS during systemic immune response
Rivest, S., Nadeau, S., Lacroix, S., & Laflamme, N. (2001) · Neuroimmune biology · doi:10.1016/s1567-7443(01)80015-6 · Cited by 4
Self-citationL'interleukine-6 dans le système nerveux central.
Vallières, L., & Rivest, S. (2000) · médecine/sciences · doi:10.4267/10608/1761 · Cited by 3
Self-citationOsborne, L., Dunai, C., Huang, Y., Egbe, F. N., Turtle, L., Michael, B. D., & Ellul, M. A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1751672 · Cited by 2
Maternal infection, cytokines and risk for schizophrenia
Gilmore, J. H., & Jarskog, L. F. (2005) · CRC Press eBooks · doi:10.3109/9780203007648-13 · Cited by 2
„Old Friends“, Immunregulation und Stressresilienz
Langgartner, D., Lowry, C. A., & Reber, S. O. (2020) · Nervenheilkunde · doi:10.1055/a-1037-0710 · Cited by 1
Neuroanatomy of Fever: Localization of Cytokine and Prostaglandin Systems in the Brain
Matsumura, K., & Kobayashi, S. (2001) · Springer eBooks · doi:10.1007/978-4-431-67035-3_33 · Cited by 1
Vallès, A. (2003) · TDX (Tesis Doctorals en Xarxa) · Cited by 1
Sabbagh, J. J. (2020) · Digital Scholarship - UNLV (University of Nevada Reno) · doi:10.34917/4478299
Brain Barriers and the Acute-Phase Response
Marques, F., Correia‐Neves, M., Carlos, J., Sousa, N., & Almeida, J. (2011) · InTech eBooks · doi:10.5772/22780
“Most of these findings originated from work on the brain parenchyma response to inflammation (Quan et al., 1998; Nadeau & Rivest, 1999); however, surprisingly, only recently were the barriers of the brain specifically considered in the overall response to peripheral inflammation.”
Reyes-Irisarri, E. (2007) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
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Rivest, S. (2002) · CRC Press eBooks · doi:10.1201/9780203908891.ch2
Self-citationYusta, G., Díaz-Peláez, E., & Muriel, C. (2007) · PubMed
Clemenzi, M. N. (2019) · TSpace (University of Toronto)
Anisman, H., & Kusnecov, A. W. (2004) · doi:10.1093/acprof:oso/9780195162851.003.0023
Psycho-Neurological and Immunological Aspects of Cushing’s Syndrome
Matos, T., Sapinho, I., Sagarribay, A., & Marques, P. (2024) · Integrated science · doi:10.1007/978-3-031-72079-6_28
Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2
Vasilache, A. M. (2015) · Linköping University medical dissertations · doi:10.3384/diss.diva-114378
“…target, presenting receptors for IL-1β (Ek et al., 2001; Ericsson et al., 1995; Konsman et al., 2004), IL-6 (Vallieres and Rivest, 1997) and TNFα (Nadeau and Rivest, 1999a) as well as intracellular cytokine activation markers like IkBα (Laflamme and Rivest, 1999; Quan et al., 1997) and SOCS3…”
BackgroundInfluentialADIPONECTIN MODULATES EXCITABILITY OF SUBFORNICAL ORGAN NEURONS AT DIFFERENT ENERGY STATES
Alim, I. (2009) · QSpace (Queen's University Library)
Metadata
- Authors
- Nadeau, S., & Rivest, S.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Rivest, Serge
- ORCID
- Rivest, Serge
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-01
- Volume
- 58
- Issue
- 1
- Pages
- 61-77
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2049819816
- Cited by
- 142
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 1
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TNF-α, TNF-alpha gene expression, lipopolysaccharide, endotoxemia, brain, pituitary gland, choroid plexus, circumventricular organs, microglia, CD14, neuroinflammation, turpentine, neurohypophysis, phagocytes, CNS immune response, rats, in situ hybridization
- MeSH terms
- Animals, Antibody Formation, Brain, Dose-Response Relationship, Drug, Gene Expression Regulation, Genetic Code, Inflammation, Injections, Intramuscular, Lipopolysaccharides, Male, Models, Biological, Pituitary Gland, Tumor Necrosis Factor-alpha, Turpentine, Rats, Sprague-Dawley, Rats
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