The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging
Abstract
In normal brain aging, CNS resident macrophages exhibit increased expression of major histocompatibility complex (MHC) II expression. However, the transcriptional basis for this observation has not been clarified nor have age-related alterations in pivotal pro-inflammatory genes been characterized. Age-related mRNA alterations in MHC II, MHC II accessory molecules and several pro-inflammatory mediators were measured in older (24 months) and younger (3 months) male F344xBN F1 rats. Real time RT-PCR was utilized to measure steady state mRNA levels in hippocampus. Older as compared to younger animals exhibited increased mRNA levels of MHC II, CD86, CIITA and IFN-gamma. Furthermore, IL-10 and CD200 mRNA, molecules that down-regulate macrophage activation, was decreased in older animals. The present results indicate that normal brain aging is characterized by a shift towards a pro-inflammatory microenvironment in the CNS.
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“Associated with these morphological alterations are biochemical changes, such as elevated expression of antigen presentation molecules (MHCII), Toll-like receptors, pro-inflammatory cytokines (IL-1β), reduced expression of regulatory molecules (CX3CR1 and CD200R) (Frank et al, 2006;Maher et al, 2004), DNA methylation changes and telomere shortening (Flanary and Streit, 2003;Zannas et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Frank et al, 2006
In the citing paper
“Microglia under normal aging (ie, aging in absence of neurodegeneration) showed upregulation of genes associated with antigen presentation, such as MHCII, CD86, and CIITA (Frank et al, 2006;Godbout et al, 2005;VanGuilder et al, 2011), and suppression of anti-inflammatory genes, such as IL-10 and CD200 (Frank et al, 2006).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Frank et al, 2006
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Cites
Analysis 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
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302
Single-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
A 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
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
The Immunological Synapse: A Molecular Machine Controlling T Cell Activation
Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M., & Dustin, M. L. (1999) · Science · doi:10.1126/science.285.5425.221 · Cited by 3,110
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874
Dong, Y., & Benveniste, E. N. (2001) · Glia · doi:10.1002/glia.1107 · Cited by 1,325
Aloisi, F. (2001) · Glia · doi:10.1002/glia.1106 · Cited by 1,310
Streit, W. J., Walter, S. A., & Pennell, N. A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00069-0 · Cited by 1,096
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Harry, G. J., & McPherson, C. A. (2016) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-319-33486-8_3
Henry, C. J. (2011) · OhioLink ETD Center (Ohio Library and Information Network)
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Crichton, R. R., & Ward, R. J. (2013) · Wiley eBooks · doi:10.1002/9781118553480.ch03
Couch, C., Alawieh, A. M., Toutonji, A., Atkinson, C., & Tomlinson, S. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4100295
Bruszt, N., Bali, Z. K., Nagy, L. V., Bodó, K., Engelmann, P., Ledneczki, I., Némethy, Z., Lendvai, B., & Hernádi, I. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.20.558650
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Hoogland, I. C. M., Yik, J., Westhoff, D., Engelen-Lee, J.-Y., Seron, M. V., Man, W. K., Houben-Weerts, J. H. P. M., Tanck, M. W. T., van Westerloo, D. J., van der Poll, T., et al. (2022) · Figshare · doi:10.6084/m9.figshare.19589097
Llorián‐Salvador, M., de la Fuente, A. G., McMurran, C. E., Dashwood, A., Dooley, J., Liston, A., Peñalva, R. G., Dombrowski, Y., Stitt, A. W., & Fitzgerald, D. C. (2024) · Figshare · doi:10.6084/m9.figshare.25556534
Llorián‐Salvador, M., de la Fuente, A. G., McMurran, C. E., Dashwood, A., Dooley, J., Liston, A., Peñalva, R. G., Dombrowski, Y., Stitt, A. W., & Fitzgerald, D. C. (2024) · Figshare · doi:10.6084/m9.figshare.26702587
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Ben-Azu, B., Gargus, M., Verkhratsky, A., & Tremblay, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27340-7.00007-3
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Marcand-Sauvant, J. (2010) · theses.fr (ABES) · doi:10.70675/2277079ez602ez4b12za4b9z8d9889d96845
Guerin, S. P., Sanchez, K., Verma, A., Salem, N. A., Mayfield, R. D., & Fonken, L. K. (2026) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2026.578947
Xu, Z.-Q., Li, X.-W., Wang, G.-C., Wang, X., Wu, J., Wu, M.-H., Wu, M.-H., Wang, G.-M., & Zhang, M.-Y. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02565-2
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Metadata
- Authors
- Frank, M. G., Barrientos, R. M., Biedenkapp, J. C., Rudy, J. W., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Frank, Matthew G.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 27
- Issue
- 5
- Pages
- 717-722
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2078514181
- Cited by
- 327
- References
- 51
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 12 · 2023: 15 · 2022: 20 · 2021: 24 · 2020: 21 · 2019: 17 · 2018: 19 · 2017: 13 · 2016: 24 · 2015: 18 · 2014: 17 · 2013: 13 · 2012: 18
- FWCI
- 6.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5f32mh064339-03)
- National Institute of Mental Health (5 F32 MH064339-03)
- National Institute on Drug Abuse (F32DA015591)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- brain aging, MHC class II, microglia, pro-inflammatory genes, hippocampus, CD86, CIITA, interferon-gamma, IL-10, CD200, macrophage activation, neuroinflammation, gene expression
- MeSH terms
- Aging, Animals, Brain, Genes, MHC Class II, Inflammation, Male, Neurons, Rats, Inbred F344, Receptors, Immunologic, RNA, Messenger, Antigens, CD, Up-Regulation, DNA Primers, DNA, Complementary, Gene Expression Regulation, Developmental, Reverse Transcriptase Polymerase Chain Reaction, Rats
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