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Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.

Berg A, Zelano J, Pekna M, Wilhelmsson U, Pekny M, Cullheim S - PLoS ONE (2013)

Bottom Line: The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process.After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete.Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.

ABSTRACT
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.

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Long-term recovery of function after SNC.(A–C) Grip strength. Grip strength was complete in 20% of WT (n = 5) and none of the GFAP–/–Vim–/– (n = 5) at 13 days, in 80% of WT and 40% of GFAP–/–Vim–/– at 20 days, and in all mice at 27 days. (D) Footfaults, WT mice performed better than GFAP–/–Vim–/– mice at 20 and 27 days after SNC, but no difference was seen at 33 days. (E, F) With respect to toe spread (E) and intermediary toe-spread (F), WT mice had a better recovery at 27 days after SNC; however, at 33 days, all mice had recovered to preoperative levels. Error bars indicate SEM. *p <0.05 (unpaired t test), ns =  non-significant.
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pone-0079395-g004: Long-term recovery of function after SNC.(A–C) Grip strength. Grip strength was complete in 20% of WT (n = 5) and none of the GFAP–/–Vim–/– (n = 5) at 13 days, in 80% of WT and 40% of GFAP–/–Vim–/– at 20 days, and in all mice at 27 days. (D) Footfaults, WT mice performed better than GFAP–/–Vim–/– mice at 20 and 27 days after SNC, but no difference was seen at 33 days. (E, F) With respect to toe spread (E) and intermediary toe-spread (F), WT mice had a better recovery at 27 days after SNC; however, at 33 days, all mice had recovered to preoperative levels. Error bars indicate SEM. *p <0.05 (unpaired t test), ns =  non-significant.

Mentions: Six days after SNC, WT and GFAP–/–Vim–/– mice had no grip function. At 13 days, grip strength was partial in 4 of 5 WT mice and complete in 1, but was partial in all 5 GFAP–/–Vim–/– mice. At 20 days, grip strength was complete in 4 of 5 WT mice and in 2 of 5 GFAP–/–Vim–/– mice. After 27 days, both strains had full grip strength (Fig. 4 A-C).


Axonal regeneration after sciatic nerve lesion is delayed but complete in GFAP- and vimentin-deficient mice.

Berg A, Zelano J, Pekna M, Wilhelmsson U, Pekny M, Cullheim S - PLoS ONE (2013)

Long-term recovery of function after SNC.(A–C) Grip strength. Grip strength was complete in 20% of WT (n = 5) and none of the GFAP–/–Vim–/– (n = 5) at 13 days, in 80% of WT and 40% of GFAP–/–Vim–/– at 20 days, and in all mice at 27 days. (D) Footfaults, WT mice performed better than GFAP–/–Vim–/– mice at 20 and 27 days after SNC, but no difference was seen at 33 days. (E, F) With respect to toe spread (E) and intermediary toe-spread (F), WT mice had a better recovery at 27 days after SNC; however, at 33 days, all mice had recovered to preoperative levels. Error bars indicate SEM. *p <0.05 (unpaired t test), ns =  non-significant.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815133&req=5

pone-0079395-g004: Long-term recovery of function after SNC.(A–C) Grip strength. Grip strength was complete in 20% of WT (n = 5) and none of the GFAP–/–Vim–/– (n = 5) at 13 days, in 80% of WT and 40% of GFAP–/–Vim–/– at 20 days, and in all mice at 27 days. (D) Footfaults, WT mice performed better than GFAP–/–Vim–/– mice at 20 and 27 days after SNC, but no difference was seen at 33 days. (E, F) With respect to toe spread (E) and intermediary toe-spread (F), WT mice had a better recovery at 27 days after SNC; however, at 33 days, all mice had recovered to preoperative levels. Error bars indicate SEM. *p <0.05 (unpaired t test), ns =  non-significant.
Mentions: Six days after SNC, WT and GFAP–/–Vim–/– mice had no grip function. At 13 days, grip strength was partial in 4 of 5 WT mice and complete in 1, but was partial in all 5 GFAP–/–Vim–/– mice. At 20 days, grip strength was complete in 4 of 5 WT mice and in 2 of 5 GFAP–/–Vim–/– mice. After 27 days, both strains had full grip strength (Fig. 4 A-C).

Bottom Line: The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process.After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete.Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.

ABSTRACT
Peripheral axotomy of motoneurons triggers Wallerian degeneration of injured axons distal to the lesion, followed by axon regeneration. Centrally, axotomy induces loss of synapses (synaptic stripping) from the surface of lesioned motoneurons in the spinal cord. At the lesion site, reactive Schwann cells provide trophic support and guidance for outgrowing axons. The mechanisms of synaptic stripping remain elusive, but reactive astrocytes and microglia appear to be important in this process. We studied axonal regeneration and synaptic stripping of motoneurons after a sciatic nerve lesion in mice lacking the intermediate filament (nanofilament) proteins glial fibrillary acidic protein (GFAP) and vimentin, which are upregulated in reactive astrocytes and Schwann cells. Seven days after sciatic nerve transection, ultrastructural analysis of synaptic density on the somata of injured motoneurons revealed more remaining boutons covering injured somata in GFAP(-/-)Vim(-/-) mice. After sciatic nerve crush in GFAP(-/-)Vim(-/-) mice, the fraction of reinnervated motor endplates on muscle fibers of the gastrocnemius muscle was reduced 13 days after the injury, and axonal regeneration and functional recovery were delayed but complete. Thus, the absence of GFAP and vimentin in glial cells does not seem to affect the outcome after peripheral motoneuron injury but may have an important effect on the response dynamics.

Show MeSH
Related in: MedlinePlus