Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

Janelsins, Michelle C; Mastrangelo, Michael A; Oddo, Salvatore; LaFerla, Frank M; Federoff, Howard J; Bowers, William J

doi:10.1186/1742-2094-2-23

Cited by 261Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

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Janelsins, Michelle C, Mastrangelo, Michael A, Oddo, Salvatore, LaFerla, Frank M, Federoff, Howard J, Bowers, William J·2005·Journal of Neuroinflammation

DOI 10.1186/1742-2094-2-23PMC PMC1276812

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Abstract

Background: Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ) deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Methods: Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. Results: We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Conclusion: Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.

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CCL2 and TNFα mRNA levels were elevated in APPPS1;Cx3cr1+/+ mouse brain.
“Similar to previous findings in AD brains and mouse models, 39 -42 the levels of CCL2 and TNF␣ mRNAs were elevated in the APPPS1;Cx3cr1 ϩ/ϩ mouse brain.”
From CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models (2010) · cites this paper as [42]

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248. Revealing the Role(s) of TNF-alpha in Early Alzheimer's Disease Via rAAV-Mediated Hippocampal Gene Transfer in a Triple Transgenic Mouse Model
Janelsins, M. C., Mastrangelo, M. A., Park, K. M., Fowlkes, K. L., Kinsky, M., Narrow, W. C., Oddo, S., LaFerla, F. M., Federoff, H. J., & Bowers, W. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.08.275
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P1‐318: Ablated TNF receptor expression differentially affects microglial activation and amyloid deposition in the 3xTg‐AD mouse model
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Journal of Neuroinflammation BioMed Central
Janelsins, M. C., Mastrangelo, M. A., Oddo, S., Laferla, F. M., Federoff, H. J., & Bowers, W. J. (2005)
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Chronic Neuron-Specific Tumor Necrosis Factor-Alpha Expression Enhances the Local Inflammatory Environment Ultimately Leading to Neuronal Death in 3xTg-AD Mice
Janelsins, M. C., Mastrangelo, M. A., Park, K. M., Sudol, K. L., Narrow, W. C., Oddo, S., LaFerla, F. M., Callahan, L. M., Federoff, H. J., & Bowers, W. J. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.080528 · Cited by 220 · see citing works
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O4‐02‐06: Expression of IL‐1β and TNF‐α in Alzheimer's pathology in mice
Finsen, B. R. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2011.05.1977

Authors: Janelsins, M. C., Mastrangelo, M. A., Oddo, S., LaFerla, F. M., Federoff, H. J., & Bowers, W. J.
Affiliations: University of Rochester Medicine (US)
University of California, Irvine (US)
Corresponding author: Bowers, William J
ORCID: Janelsins, Michelle C
Oddo, Salvatore
LaFerla, Frank M
Federoff, Howard J
Bowers, William J
Venue: Journal of Neuroinflammation
Publisher: Springer Science and Business Media LLC
Published: 2005-10-18
Volume: 2
Issue: 1
Pages: 23-23
ISSN: 1742-2094 (ISSN-L)
DOI: 10.1186/1742-2094-2-23
PMC: PMC1276812
OpenAlex: W2163115168
Cited by: 260
References: 41
Citations by year: 2026: 2 · 2025: 9 · 2024: 22 · 2023: 13 · 2022: 13 · 2021: 8 · 2020: 18 · 2019: 13 · 2018: 14 · 2017: 14 · 2016: 12 · 2015: 18 · 2014: 11 · 2013: 13 · 2012: 15
FWCI: 4.44
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Journal of Neuroinflammation (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
National Institute on Aging (R01AG020204, R01AG023593)
National Institute of Neurological Disorders and Stroke (F31NS049995)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: Alzheimer's disease, microglial activation, neuroinflammation, 3xTg-AD mice, entorhinal cortex, hippocampus, amyloid-beta deposition, TNF-α, MCP-1, microglia/macrophages, F4/80, neurofibrillary tangles

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Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

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