Impact of aging on meningeal gene expression

Fluids and Barriers of the CNS

Research

Albert Neutzner¹  Corina Kohler¹  Hanspeter E. Killer¹  Melanie Neutzner¹  Stephan Frank² 

[1]Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, 4031, Basel, Switzerland

[2]Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland

关键词: Meninges;    Aging;    Cerebrospinal fluid;    Neuroimmunology;    Neurodegeneration;    Inflammation;    Brain;   

DOI  :  10.1186/s12987-023-00412-9

 received in 2022-11-07, accepted in 2023-01-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsWe 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.ResultsAging 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.ConclusionsAging 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.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 1

Fig. 2

Fig. 4

Fig. 1

Fig. 1

40249_2023_1061_Article_IEq16.gif

Fig. 6