Adult CST‐null mice maintain an increased number of oligodendrocytes

Shroff, Seema; Pomicter, Anthony D.; Chow, Woon N.; Fox, Michael A.; Colello, Raymond J.; Henderson, Scott C.; Dupree, Jeffrey L.

doi:10.1002/jnr.22003

Cited by 35 publications

(32 citation statements)

References 60 publications

(96 reference statements)

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“…Mice were processed for standard electron microscopic analysis as previously described with slight modifications 18,19 . Briefly, following transcardial perfusion of appropriately aged mice, brains were harvested and vibratome sectioned to locate the regions of interest (PFC, nucleus accumbens and anterior commissure).…”

Section: Methodsmentioning

confidence: 99%

Impaired adult myelination in the prefrontal cortex of socially isolated mice

et al. 2012

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Protracted social isolation of adult mice induced behavioral, transcriptional and ultrastructural changes in oligodendrocytes of the prefrontal cortex (PFC) and impaired adult myelination. Social re-integration was sufficient to normalize behavioral and transcriptional changes. Short periods of isolation affected chromatin and myelin, but did not induce behavioral changes. Thus, myelinating oligodendrocytes in the adult PFC respond to social interaction with chromatin changes, suggesting that myelination acts as a form of adult plasticity.

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Section: Methodsmentioning

confidence: 99%

Impaired adult myelination in the prefrontal cortex of socially isolated mice

et al. 2012

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“…All mice used in this study were generated and genotyped as previously described [13; 31]. Although the myelin paranode degenerates with age in the CST KO mice, minimal paranodal ultrastructural disruption is observed in 15 day old mutants as paranodal loops are tightly packed with adjacent loops and oriented toward the axolemma [15].…”

Section: Methodsmentioning

confidence: 99%

Nfasc155H and MAG are Specifically Susceptible to Detergent Extraction in the Absence of the Myelin Sphingolipid Sulfatide

et al. 2013

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Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that deteriorate with age. Similar instability also occurs in mice that lack contactin, contactin-associated protein or neurofascin155 (Nfasc155), the proteins that cluster in the paranode and form the junctional complex that mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not been shown to be enriched in the paranode nor has a sulfatide paranodal binding partner been identified; thus, it remains unclear how the absence of sulfatide results in compromised paranode integrity., Using an in situ extraction procedure, it has been reported that the absence of the myelin sphingolipids, galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to detergent extraction. Here, employing a similar approach, we demonstrate that in the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is susceptible to detergent extraction. Furthermore, we use this in situ approach to show that stable association of myelin-associate glycoprotein (MAG) with the myelin membrane is sulfatide dependent while the membrane associations of myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide phosphodiesterase are sulfatide independent. These findings indicate that myelin proteins maintain their membrane associations by different mechanisms. Moreover, the myelin proteins that cluster in the paranode and require sulfatide mediate myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for maintaining Nfasc155 and MAG associations is intriguing since the fatty acid composition of sulfatide is altered and paranodal ultrastructure is compromised in multiple sclerosis. Thus, our findings present a potential link between sulfatide perturbation and myelin deterioration in multiple sclerosis.

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“…Spinal cord samples spanning cervical regions C4-C6 from 15 day, 1 month, 8 month, 12 month, 17 month and 22-month-old mice were prepared for electron microscopic examination and analyzed on a JEOL JEM1230 transmission electron microscope equipped with a Gatan Ultrascan 4,000SP CCD camera as previously described (Dupree et al, 1998; Shroff et al, 2009). …”

Section: Methodsmentioning

confidence: 99%

“…Cervical spinal cord samples were cryosectioned, immunolabeled with the appropriate primary and fluorescently labeled secondary antibodies, and imaged using a Leica TCS-SP2 AOBS laser scanning confocal microscope (Leica Microsystems, Inc., Exton, PA) as previously described (Dupree et al, 1999; Dupree et al, 2004; Pomicter et al, 2010; Shroff et al, 2009). Two spinal cord samples were collected per animal; one sample was embedded for longitudinal analysis while the second sample was used for transverse analysis.…”

Section: Methodsmentioning

confidence: 99%

Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system

Shepherd

Pomicter

Velazco

et al. 2012

Neurobiology of Aging

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Paranodal axo-glial junctional complexes anchor the myelin sheath to the axon and breakdown of these complexes presumably facilitates demyelination. Myelin deterioration is also prominent in the aging central nervous system (CNS); however, the stability of the paranodal complexes in the aged CNS has not been examined. Here, we show that transverse bands, prominent components of paranodal junctions, are significantly reduced in the aged CNS; however, the number of paired clusters of both myelin and axonal paranodal proteins is not altered. Ultrastructural analyses also reveal that thicker myelin sheaths display a “piling” of paranodal loops, the cytoplasm-containing sacs that demarcate the paranode. Loops involved in piling are observed throughout the paranode and are not limited to loops positioned in either the nodal- or juxtanodal-most regions. Here, we propose that as myelination continues, previously anchored loops lose their transverse bands and recede away from the axolemma. Newly juxtaposed loops then lose their transverse bands, move laterally to fill in the gap left by the receded loops and finally reform their transverse bands. This paranodal reorganization results in conservation of paranodal length, which may be important in maintaining ion channel spacing and axonal function. Furthermore, we propose that transverse band reformation is less efficient in the aged CNS, resulting in the significant reduction of these junctional components. Although demyelination was not observed, we propose that loss of transverse bands facilitates myelin degeneration and may predispose the aged CNS to a poorer prognosis following a secondary insult.

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Adult CST‐null mice maintain an increased number of oligodendrocytes

Cited by 35 publications

References 60 publications

Impaired adult myelination in the prefrontal cortex of socially isolated mice

Impaired adult myelination in the prefrontal cortex of socially isolated mice

Nfasc155H and MAG are Specifically Susceptible to Detergent Extraction in the Absence of the Myelin Sphingolipid Sulfatide

Paranodal reorganization results in the depletion of transverse bands in the aged central nervous system

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