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Cited by 58Neuroinflammation and Neurodegeneration MechanismsInflammasome and immune disordersTryptophan and brain disorders

Age and Sex Influence the Neuro-inflammatory Response to a Peripheral Acute LPS Challenge

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Murtaj, Valentina, Belloli, Sara, Di Grigoli, Giuseppe, Pannese, Maria, Ballarini, Elisa, Rodriguez-Menendez, Virginia, Marmiroli, Paola, Cappelli, Andrea +5 more·2019·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2019.00299PMC PMC6848890
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Abstract

Aging is associated with an exaggerated response to peripheral inflammatory challenges together with behavioral and cognitive deficits. Studies considering both age and sex remain limited, despite sex dimorphism of astrocytes and microglial cells is largely recognized. To fill this knowledge gap, we investigated the effect of a single intraperitoneal lipopolysaccharide (LPS) administration in adult and aged mice. We assessed the expression of different inflammatory mediators, and the microglial response through binding of [18F]-VC701 tracer to translocator protein (TSPO) receptors in the male and female brain. Aged female brain showed a higher pro-inflammatory response to LPS compared to adult female and to aged male, as revealed by ex vivo binding to TSPO receptors and pro-inflammatory mediator transcript levels. The highest astroglial reaction was observed in the brain of aged females. Differently to the other groups of animals, in aged males LPS challenge did not affect transcription of triggering receptor expressed on myeloid cells 2 (TREM2). In conclusion, our study shows that in the mouse brain the neuroinflammatory response to an acute peripheral insult is sex and age dependent. Moreover, our results might set the basis for further studies aimed at identifying sex related targets involved in the modulation of the aberrant neuro-inflammatory response that characterizes aging. This knowledge could be relevant for the treatment of conditions such as delirium and dementia.

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  • Female microglia exhibit higher pro-inflammatory responses compared to age-matched male cells.

    “with female cells exhibiting higher pro-inflammatory responses compared to age-matched male cells.67,68”

    From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [67]

    The Discussion reports a stronger pro-inflammatory response to LPS in aged female than aged male mouse brains, and the Results identify higher levels of particular inflammatory transcripts in aged females. The claim omits the aged-mouse and acute LPS-challenge conditions and presents a brain-level finding as a general property of female microglial cells; the Discussion also describes adult male microglia as more poised to inflammatory reactions. (LLM, conf=0.87)

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Authors
Murtaj, V., Belloli, S., Di Grigoli, G., Pannese, M., Ballarini, E., Rodriguez-Menendez, V., Marmiroli, P., Cappelli, A., Masiello, V., Monterisi, C., Bellelli, G., Panina-Bordignon, P., & Moresco, R. M.
Affiliations
  • IRCCS Ospedale San Raffaele (IT)
  • Institute of Molecular Bioimaging and Physiology (IT)
  • University of Milano-Bicocca (IT)
  • University of Siena (IT)
  • Azienda Ospedaliera San Gerardo (IT)
Corresponding author
Moresco, Rosa Maria
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2019-11-05
Volume
11
Pages
299-299
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2019.00299
PMC
PMC6848890
OpenAlex
W2985276039
Cited by
58
References
12
Citations by year
2026: 9 · 2025: 10 · 2024: 10 · 2023: 9 · 2022: 8 · 2021: 9 · 2020: 3
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
Funders
Ministero dell’Istruzione, dell’Universitáa e della Ricerca (CTN01 00177 165430)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
neuroinflammation, aging, sex differences, lipopolysaccharide challenge, microglial activation, astrocytes, translocator protein (TSPO), TREM2, pro-inflammatory mediators, peripheral inflammation, delirium, dementia

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