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PMID:22337502

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Citation

Verdier, V, Csárdi, G, de Preux-Charles, AS, Médard, JJ, Smit, AB, Verheijen, MH, Bergmann, S and Chrast, R (2012) Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways. Glia 60:751-60

Abstract

Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.

Links

PubMed Online version:10.1002/glia.22305

Keywords

Animals; Animals, Newborn; Cellular Senescence/immunology; Lipid Metabolism/immunology; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Nerve Fibers, Myelinated/immunology; Nerve Fibers, Myelinated/metabolism; Neural Pathways/immunology; Neural Pathways/metabolism; Neuroglia/cytology; Neuroglia/immunology; Neuroglia/metabolism; Sciatic Nerve/immunology; Sciatic Nerve/metabolism; Signal Transduction/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SCAP

acts_upstream_of_or_within

GO:0006955: immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2148743

P

Seeded From UniProt

complete

MOUSE:SCAP

acts_upstream_of_or_within

GO:0044255: cellular lipid metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2148743

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0022011: myelination in peripheral nervous system

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447704

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0044255: cellular lipid metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447704

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0006955: immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447704

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0007422: peripheral nervous system development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447704

P

Seeded From UniProt

complete

MOUSE:PMP22

acts_upstream_of_or_within

GO:0010259: multicellular organism aging

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2447704

P

Seeded From UniProt

complete

MOUSE:LPIN1

acts_upstream_of_or_within

GO:0006955: immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3799353

P

Seeded From UniProt

complete

MOUSE:LPIN1

acts_upstream_of_or_within

GO:0044255: cellular lipid metabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3799353

P

Seeded From UniProt

complete

Notes

See also

References

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