Limits...
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.

Show MeSH

Related in: MedlinePlus

Reinnervation of the gastrocnemius muscle.At 13 days after SNC, the number of reinnervated postsynaptic clusters (i.e. synaptophysin (red, middle column) and α-bungarotoxin (green, left column) -positive clusters, and merged in right column) was higher in WT mice (n = 5) than in GFAP–/–Vim–/– mice (n = 5) (A and C). Arrows indicate reinnervated postsynaptic sites. At 22 days, there was no statistical difference between the two groups (B, C). The number of postsynaptic sites was similar in WT and GFAP–/–Vim–/– mice. In D, the postsynaptic sites were quantified on α-bungarotoxin stained sections from uninjured mice, and from lesioned mice 13 and 22 days post SNT. No difference was seen at any of the time points. Error bars indicates SEM. *p<0.05 (one-way ANOVA), ns =  non-significant. Scale bar, 100 µm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3815133&req=5

pone-0079395-g007: Reinnervation of the gastrocnemius muscle.At 13 days after SNC, the number of reinnervated postsynaptic clusters (i.e. synaptophysin (red, middle column) and α-bungarotoxin (green, left column) -positive clusters, and merged in right column) was higher in WT mice (n = 5) than in GFAP–/–Vim–/– mice (n = 5) (A and C). Arrows indicate reinnervated postsynaptic sites. At 22 days, there was no statistical difference between the two groups (B, C). The number of postsynaptic sites was similar in WT and GFAP–/–Vim–/– mice. In D, the postsynaptic sites were quantified on α-bungarotoxin stained sections from uninjured mice, and from lesioned mice 13 and 22 days post SNT. No difference was seen at any of the time points. Error bars indicates SEM. *p<0.05 (one-way ANOVA), ns =  non-significant. Scale bar, 100 µm.

Mentions: Next, we investigated the degree of reinnervation of the denervated muscle. At 13 days after SNC, double staining for the postsynaptic marker α-bungarotoxin and the presynaptic marker synaptophysin revealed a difference in the fraction of reinnervated motor endplates: 36.0 ±1.9% in WT mice vs 27.9 ±2.5% in GFAP–/–Vim–/– mice (p<0.05) (Fig. 7A, C). At 22 days, no difference was seen, although the tendency persisted (Fig. 7B-C). The density of postsynaptic clusters did not differ between WT and GFAP–/–Vim–/– mice at 13 or 22 days (Fig. 7D).


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)

Reinnervation of the gastrocnemius muscle.At 13 days after SNC, the number of reinnervated postsynaptic clusters (i.e. synaptophysin (red, middle column) and α-bungarotoxin (green, left column) -positive clusters, and merged in right column) was higher in WT mice (n = 5) than in GFAP–/–Vim–/– mice (n = 5) (A and C). Arrows indicate reinnervated postsynaptic sites. At 22 days, there was no statistical difference between the two groups (B, C). The number of postsynaptic sites was similar in WT and GFAP–/–Vim–/– mice. In D, the postsynaptic sites were quantified on α-bungarotoxin stained sections from uninjured mice, and from lesioned mice 13 and 22 days post SNT. No difference was seen at any of the time points. Error bars indicates SEM. *p<0.05 (one-way ANOVA), ns =  non-significant. Scale bar, 100 µm.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0079395-g007: Reinnervation of the gastrocnemius muscle.At 13 days after SNC, the number of reinnervated postsynaptic clusters (i.e. synaptophysin (red, middle column) and α-bungarotoxin (green, left column) -positive clusters, and merged in right column) was higher in WT mice (n = 5) than in GFAP–/–Vim–/– mice (n = 5) (A and C). Arrows indicate reinnervated postsynaptic sites. At 22 days, there was no statistical difference between the two groups (B, C). The number of postsynaptic sites was similar in WT and GFAP–/–Vim–/– mice. In D, the postsynaptic sites were quantified on α-bungarotoxin stained sections from uninjured mice, and from lesioned mice 13 and 22 days post SNT. No difference was seen at any of the time points. Error bars indicates SEM. *p<0.05 (one-way ANOVA), ns =  non-significant. Scale bar, 100 µm.
Mentions: Next, we investigated the degree of reinnervation of the denervated muscle. At 13 days after SNC, double staining for the postsynaptic marker α-bungarotoxin and the presynaptic marker synaptophysin revealed a difference in the fraction of reinnervated motor endplates: 36.0 ±1.9% in WT mice vs 27.9 ±2.5% in GFAP–/–Vim–/– mice (p<0.05) (Fig. 7A, C). At 22 days, no difference was seen, although the tendency persisted (Fig. 7B-C). The density of postsynaptic clusters did not differ between WT and GFAP–/–Vim–/– mice at 13 or 22 days (Fig. 7D).

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