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Fibroblasts that reside in mouse and frog injured peripheral nerves produce apolipoproteins
A Saada1, A Dunaevsky-Hutt, A Aamar
1Department of Anatomy and Embryology, Hebrew University Medical School, Jerusalem, Israel.
Abstract:
Apolipoprotein synthesis and secretion is upregulated in wallerian degenerating peripheral nerves. A commonly expressed view has been that macrophages are solely responsible for their production. In the present study we provide evidence that (1) nerve-derived fibroblasts contribute to apolipoprotein production, (2) apolipoprotein production is confined to regions where myelin destruction and phagocytosis occur, and (3) some experimental procedures are detrimental for the production of apolipoproteins. Apolipoprotein production was studied in C57BL/6/NHSD (N) and C57/BL/6-WLD/OLA/NHSD (W) mice that display, respectively, rapid and slow progression of wallerian degeneration. In N nerves, apolipoprotein E (apo-E) is produced during in vitro and in vivo degeneration, and in vivo after freeze damage. In W nerves, apo-E is produced at the injury region where degeneration occurs but not farther distally where degeneration fails to develop. Apo-E is also produced in W nerves during in vitro degeneration and in vivo after freeze damage. In culture, N and W mice nerve-derived fibroblasts, but neither macrophages nor Schwann cells produced apo-E. Two apolipoproteins are produced in in vivo wallerian degenerating and freeze-damaged frog nerves, i.e., apo-39 and apo-29. Only apo-39 is produced in in vitro degenerating nerves. Neither apo-39 nor apo-29 is produced during in vivo degeneration in diffusion chambers. In culture, apo-39 is produced by nerve-derived fibroblasts and macrophages but not by Schwann cells.
Insights
Nerve-derived fibroblasts, not just macrophages, produce apolipoproteins during Wallerian degeneration. This production is localized to myelin breakdown sites and can be affected by experimental conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Wallerian degeneration involves peripheral nerve breakdown.
- Apolipoprotein synthesis is upregulated during this process.
- Macrophages were previously thought to be the sole producers of apolipoproteins.
Purpose of the Study:
- To investigate the cellular sources of apolipoprotein production during Wallerian degeneration.
- To determine the spatial and experimental conditions affecting apolipoprotein synthesis.
Main Methods:
- Studied apolipoprotein E (apo-E) production in mice with rapid (N) and slow (W) Wallerian degeneration.
- Utilized in vitro and in vivo degeneration models, including freeze damage and diffusion chambers.
- Analyzed apolipoprotein production by nerve-derived fibroblasts, macrophages, and Schwann cells in culture.
Main Results:
- Nerve-derived fibroblasts produce apo-E in both mouse and frog models.
- Apolipoprotein production is concentrated in areas of myelin destruction and phagocytosis.
- Certain experimental methods, like diffusion chambers, inhibit apolipoprotein synthesis.
Conclusions:
- Nerve-derived fibroblasts are significant contributors to apolipoprotein production during Wallerian degeneration.
- Apolipoprotein synthesis is spatially regulated and dependent on the degeneration microenvironment.
- Experimental design critically influences the study of apolipoprotein production in nerve injury.