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Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling.

Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD - Neuron (2013)

Bottom Line: We conclude that adult-born OLs in the optic nerve are engaged in myelin remodeling, either replacing OLs that die in service or intercalating among existing myelin sheaths.The latter would predict that average internode length should decrease with age.Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life.

View Article: PubMed Central - PubMed

Affiliation: Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.

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Adult-Born OLs Make Compact Myelin(A) An illustrative electron micrograph of a myelinated axon in the P60 optic nerve. The external cytoplasmic tongue process has been pseudo-colored yellow.(B) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P30+30 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB reaction product identifies the mGFP+ cytoplasmic tongue of the corresponding myelin internode (indicated by an arrowhead).(C) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB+ cytoplasmic tongue is indicated (arrowhead).(D) A higher-magnification image showing compact myelin synthesized by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve.(E) A scatterplot of axon diameter versus g-ratio for mGFP-negative myelinated axons in the P60 and P185 mouse optic nerves.(F) The equivalent scatterplot for axons myelinated by recently formed (mGFP+) OLs in P30+30 and P120+65 Pdgfra-CreERT2: Tau-mGFP nerves.(G) Immunogold labeling of late-born mGFP+ OLs (born P120-P185) confirms that mGFP is restricted to the external tongue (outlined in yellow) and does not enter the myelin sheath. (H) Lower magnification of (G). Scale bars represent 200 nm.
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fig7: Adult-Born OLs Make Compact Myelin(A) An illustrative electron micrograph of a myelinated axon in the P60 optic nerve. The external cytoplasmic tongue process has been pseudo-colored yellow.(B) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P30+30 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB reaction product identifies the mGFP+ cytoplasmic tongue of the corresponding myelin internode (indicated by an arrowhead).(C) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB+ cytoplasmic tongue is indicated (arrowhead).(D) A higher-magnification image showing compact myelin synthesized by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve.(E) A scatterplot of axon diameter versus g-ratio for mGFP-negative myelinated axons in the P60 and P185 mouse optic nerves.(F) The equivalent scatterplot for axons myelinated by recently formed (mGFP+) OLs in P30+30 and P120+65 Pdgfra-CreERT2: Tau-mGFP nerves.(G) Immunogold labeling of late-born mGFP+ OLs (born P120-P185) confirms that mGFP is restricted to the external tongue (outlined in yellow) and does not enter the myelin sheath. (H) Lower magnification of (G). Scale bars represent 200 nm.

Mentions: Although CC1 labeling demonstrates OL differentiation, it does not prove that those OLs form myelin sheaths. To identify newly formed myelinating OLs by morphology (Butt et al., 1994; McIver et al., 2005), we crossed Pdgfra-CreERT2 with Tau-mGFP reporter mice (Hippenmeyer et al., 2005). Tau-mGFP is active in neurons and OLs but not in OPs or other neural cells (Richter-Landsberg and Gorath, 1999) and is superior to Rosa-YFP for revealing OL morphology, either because the Tau promoter is more active than Rosa or because membrane-inserted green fluorescent protein (mGFP) is better than cytoplasmic YFP at revealing slender OL cell processes including the external tongue process, although it is still excluded from compact myelin (see Figure 7).


Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling.

Young KM, Psachoulia K, Tripathi RB, Dunn SJ, Cossell L, Attwell D, Tohyama K, Richardson WD - Neuron (2013)

Adult-Born OLs Make Compact Myelin(A) An illustrative electron micrograph of a myelinated axon in the P60 optic nerve. The external cytoplasmic tongue process has been pseudo-colored yellow.(B) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P30+30 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB reaction product identifies the mGFP+ cytoplasmic tongue of the corresponding myelin internode (indicated by an arrowhead).(C) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB+ cytoplasmic tongue is indicated (arrowhead).(D) A higher-magnification image showing compact myelin synthesized by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve.(E) A scatterplot of axon diameter versus g-ratio for mGFP-negative myelinated axons in the P60 and P185 mouse optic nerves.(F) The equivalent scatterplot for axons myelinated by recently formed (mGFP+) OLs in P30+30 and P120+65 Pdgfra-CreERT2: Tau-mGFP nerves.(G) Immunogold labeling of late-born mGFP+ OLs (born P120-P185) confirms that mGFP is restricted to the external tongue (outlined in yellow) and does not enter the myelin sheath. (H) Lower magnification of (G). Scale bars represent 200 nm.
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fig7: Adult-Born OLs Make Compact Myelin(A) An illustrative electron micrograph of a myelinated axon in the P60 optic nerve. The external cytoplasmic tongue process has been pseudo-colored yellow.(B) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P30+30 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB reaction product identifies the mGFP+ cytoplasmic tongue of the corresponding myelin internode (indicated by an arrowhead).(C) An electron micrograph of an axon that has been myelinated by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve. The DAB+ cytoplasmic tongue is indicated (arrowhead).(D) A higher-magnification image showing compact myelin synthesized by an mGFP+ OL in a P120+65 Pdgfra-CreERT2: Tau-mGFP optic nerve.(E) A scatterplot of axon diameter versus g-ratio for mGFP-negative myelinated axons in the P60 and P185 mouse optic nerves.(F) The equivalent scatterplot for axons myelinated by recently formed (mGFP+) OLs in P30+30 and P120+65 Pdgfra-CreERT2: Tau-mGFP nerves.(G) Immunogold labeling of late-born mGFP+ OLs (born P120-P185) confirms that mGFP is restricted to the external tongue (outlined in yellow) and does not enter the myelin sheath. (H) Lower magnification of (G). Scale bars represent 200 nm.
Mentions: Although CC1 labeling demonstrates OL differentiation, it does not prove that those OLs form myelin sheaths. To identify newly formed myelinating OLs by morphology (Butt et al., 1994; McIver et al., 2005), we crossed Pdgfra-CreERT2 with Tau-mGFP reporter mice (Hippenmeyer et al., 2005). Tau-mGFP is active in neurons and OLs but not in OPs or other neural cells (Richter-Landsberg and Gorath, 1999) and is superior to Rosa-YFP for revealing OL morphology, either because the Tau promoter is more active than Rosa or because membrane-inserted green fluorescent protein (mGFP) is better than cytoplasmic YFP at revealing slender OL cell processes including the external tongue process, although it is still excluded from compact myelin (see Figure 7).

Bottom Line: We conclude that adult-born OLs in the optic nerve are engaged in myelin remodeling, either replacing OLs that die in service or intercalating among existing myelin sheaths.The latter would predict that average internode length should decrease with age.Consistent with that, we found that adult-born OLs elaborated much shorter but many more internodes than OLs generated during early postnatal life.

View Article: PubMed Central - PubMed

Affiliation: Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.

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