Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6 - PubMed (original) (raw)
Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6
I L Campbell et al. Proc Natl Acad Sci U S A. 1993.
Abstract
Cytokines are thought to be important mediators in physiologic and pathophysiologic processes affecting the central nervous system (CNS). To explore this hypothesis, transgenic mice were generated in which the cytokine interleukin 6 (IL-6), under the regulatory control of the glial fibrillary acidic protein gene promoter, was overexpressed in the CNS. A number of transgenic founder mice and their offspring exhibited a neurologic syndrome the severity of which correlated with the levels of cerebral IL-6 expression. Transgenic mice with high levels of IL-6 expression developed severe neurologic disease characterized by runting, tremor, ataxia, and seizure. Neuropathologic manifestations included neuro-degeneration, astrocytosis, angiogenesis, and induction of acute-phase-protein production. These findings indicate that cytokines such as IL-6 can have a direct pathogenic role in inflammatory, infectious, and neurodegenerative CNS diseases.
Similar articles
- Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6.
Molinero A, Penkowa M, Hernández J, Camats J, Giralt M, Lago N, Carrasco J, Campbell IL, Hidalgo J. Molinero A, et al. J Neuropathol Exp Neurol. 2003 Mar;62(3):315-28. doi: 10.1093/jnen/62.3.315. J Neuropathol Exp Neurol. 2003. PMID: 12638735 - Transgenic expression of interleukin 6 in the central nervous system regulates brain metallothionein-I and -III expression in mice.
Hernández J, Molinero A, Campbell IL, Hidalgo J. Hernández J, et al. Brain Res Mol Brain Res. 1997 Aug;48(1):125-31. doi: 10.1016/s0169-328x(97)00087-9. Brain Res Mol Brain Res. 1997. PMID: 9379832 - Profound increase in sensitivity to glutamatergic- but not cholinergic agonist-induced seizures in transgenic mice with astrocyte production of IL-6.
Samland H, Huitron-Resendiz S, Masliah E, Criado J, Henriksen SJ, Campbell IL. Samland H, et al. J Neurosci Res. 2003 Jul 15;73(2):176-87. doi: 10.1002/jnr.10635. J Neurosci Res. 2003. PMID: 12836160 - Transgenic models to assess the pathogenic actions of cytokines in the central nervous system.
Campbell IL, Stalder AK, Chiang CS, Bellinger R, Heyser CJ, Steffensen S, Masliah E, Powell HC, Gold LH, Henriksen SJ, Siggins GR. Campbell IL, et al. Mol Psychiatry. 1997 Mar;2(2):125-9. doi: 10.1038/sj.mp.4000225. Mol Psychiatry. 1997. PMID: 9106234 Review. - Transgenic mice and cytokine actions in the brain: bridging the gap between structural and functional neuropathology.
Campbell IL. Campbell IL. Brain Res Brain Res Rev. 1998 May;26(2-3):327-36. doi: 10.1016/s0165-0173(97)00038-6. Brain Res Brain Res Rev. 1998. PMID: 9651549 Review.
Cited by
- In situ assessment of neuroinflammatory cytokines in different stages of ovine natural prion disease.
Guijarro IM, Garcés M, Badiola JJ, Monzón M. Guijarro IM, et al. Front Vet Sci. 2024 Oct 18;11:1404770. doi: 10.3389/fvets.2024.1404770. eCollection 2024. Front Vet Sci. 2024. PMID: 39493812 Free PMC article. - Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus.
Sano F, Shigetomi E, Shinozaki Y, Tsuzukiyama H, Saito K, Mikoshiba K, Horiuchi H, Cheung DL, Nabekura J, Sugita K, Aihara M, Koizumi S. Sano F, et al. JCI Insight. 2021 May 10;6(9):e135391. doi: 10.1172/jci.insight.135391. JCI Insight. 2021. PMID: 33830944 Free PMC article. - Immunoinflammatory diseases of the central nervous system - the tale of two cytokines.
Hofer MJ, Campbell IL. Hofer MJ, et al. Br J Pharmacol. 2016 Feb;173(4):716-28. doi: 10.1111/bph.13175. Epub 2015 Jun 12. Br J Pharmacol. 2016. PMID: 25917268 Free PMC article. Review. - Chronic interleukin-6 mediated neuroinflammation decreases anxiety, and impaires spatial memory in aged female mice.
Wagnon IM, Jabur LJ, Niedermayer G, Münch G, Karl T, Chesworth R, Gyengesi E. Wagnon IM, et al. Front Neurosci. 2023 Nov 23;17:1267818. doi: 10.3389/fnins.2023.1267818. eCollection 2023. Front Neurosci. 2023. PMID: 38075266 Free PMC article. - Interleukin-6, a major cytokine in the central nervous system.
Erta M, Quintana A, Hidalgo J. Erta M, et al. Int J Biol Sci. 2012;8(9):1254-66. doi: 10.7150/ijbs.4679. Epub 2012 Oct 25. Int J Biol Sci. 2012. PMID: 23136554 Free PMC article. Review.
References
- Neuropathol Appl Neurobiol. 1981 May-Jun;7(3):237-42 - PubMed
- Neuroscience. 1993 May;54(1):15-36 - PubMed
- Mol Cell Biol. 1983 Feb;3(2):280-9 - PubMed
- J Neuroimmunol. 1985 Jun;8(4-6):283-92 - PubMed
- Science. 1986 Feb 28;231(4741):995-7 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases