Impact of aging on meningeal gene expression
Open accessAbstract
Background: The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal fluid-filled subarachnoid space and across the brain parenchyma via their connection to glymphatic structures. Meningeal fibroblasts lining and traversing the subarachnoid space have direct impact on the composition of the cerebrospinal fluid through endocytotic uptake as well as extensive protein secretion. In addition, the meninges are an active site for immunological processes and act as gatekeeper for immune cells entering the brain. During aging in mice, lymphatic drainage from the brain is less efficient contributing to neurodegenerative processes. Aging also affects the immunological status of the meninges, with increasing numbers of T cells, changing B cell make-up, and altered macrophage complement. Methods: We employed RNASeq to measure gene expression and to identify differentially expressed genes in meninges isolated from young and aged mice. Using Ingenuity pathway, GO term, and MeSH analyses, we identified regulatory pathways and cellular functions in meninges affected by aging. Results: Aging had profound impact on meningeal gene expression. Pathways related to innate as well as adaptive immunity were affected. We found evidence for increasing numbers of T and B lymphocytes and altered activity profiles for macrophages and other myeloid cells. Furthermore, expression of pro-inflammatory cytokine and chemokine genes increased with aging. Similarly, the complement system seemed to be more active in meninges of aged mice. Altered expression of solute carrier genes pointed to age-dependent changes in cerebrospinal fluid composition. In addition, gene expression for secreted proteins showed age-dependent changes, in particular, genes related to extracellular matrix composition and organization were affected. Conclusions: Aging has profound effects on meningeal gene expression; thereby affecting the multifaceted functions meninges perform to maintain the homeostasis of the central nervous system. Thus, age-dependent neurodegenerative processes and cognitive decline are potentially in part driven by altered meningeal function.
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During aging, the meninges undergo a shift towards pro-inflammatory immune responses, characterized by an increased number of T cells and B cells.
“During aging, the meninges undergo a shift towards pro-inflammatory immune responses, characterized by an increased number of T cells and B cells.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [681]
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- Authors
- Neutzner, M., Kohler, C., Frank, S., Killer, H. E., & Neutzner, A.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Neutzner, Albert
- Venue
- Fluids and Barriers of the CNS
- Published
- 2023-02-06
- Volume
- 20
- Issue
- 1
- Pages
- 12-12
- ISSN
- 2045-8118 (ISSN-L)
- PMC
- PMC9903605
- OpenAlex
- W4319296716
- Cited by
- 17
- References
- 61
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 3
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Fluids and Barriers of the CNS (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Herta-Messerli-Stiftung
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- meninges, aging, gene expression, meningeal fibroblasts, cerebrospinal fluid composition, glymphatic system, lymphatic drainage, meningeal immunity, T cells, B cells, macrophages, complement system, inflammatory cytokines, chemokines, solute carrier transporters, extracellular matrix, neurodegeneration, cognitive decline, mice
- MeSH terms
- Aging, Animals, Brain, Central Nervous System, Meninges, Gene Expression, Mice
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