The Cytoplasmic Domain of the Large Myelin-Associated Glycoprotein Isoform Is Needed for Proper CNS But Not Peripheral Nervous System Myelination

Fujita, Nobuya; Kemper, April; Dupree, Jeffrey L.; Nakayasu, Hiroyuki; Bartsch, Udo; Schachner, Melitta; Maeda, Nobuyo; Suzuki, Kinuko; Suzuki, Kazuyuki; Popko, Brian

doi:10.1523/jneurosci.18-06-01970.1998

Cited by 73 publications

(60 citation statements)

References 51 publications

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“…The time course of myelination observed in the present study is consistent with the finding of a previous study using immunostaining for the major myelin components, including MBP, that myelin formation in the gray matter and the dorsal CST starts at around P11 in rats (Schwab and Schnell, 1989). Further, Western blot studies have shown that MAG expression dramatically increases after P14 (Fujita et al, 1998;Cho et al, 2005). Our results on MAG expression are also consistent with those of the MAG mRNA expression reported previously (Jordan et al, 1989).…”

Section: Discussionsupporting

confidence: 93%

Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury

et al. 2010

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The rewiring of neural networks is a fundamental step in recovering behavioral functions after brain injury. However, there is limited potential for axonal plasticity in the adult CNS. The myelin-associated proteins Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp) are known to inhibit axonal plasticity, and thus targeting the inhibitory pathways they participate in is a potential means of promoting plasticity and functional recovery. Each of Nogo, MAG, and OMgp interacts with both the Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Here, we determined whether blocking PirB activity enhances axonal reorganization and functional recovery after cortical injury. We found that axons of the contralesional corticospinal tract sprouted into the denervated side of the cervical spinal cord after unilateral injury of the motor cortex. The extent to which this axonal reorganization occurred was far greater in mice lesioned during early postnatal days than in mice lesioned at an age when myelin had begun to form. This suggests that myelin-associated proteins might limit axonal remodeling in vivo. However, the number of sprouting fibers within either the corticospinal or corticorubral tract was not enhanced in PirB Ϫ/Ϫ mice. Blocking PirB signaling also failed to enhance functional recovery with three motor tests. Our results suggest that blocking the function of PirB is not sufficient to promote axonal reorganization or functional recovery after cortical injury.

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Section: Discussionsupporting

confidence: 93%

Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury

et al. 2010

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“…As another sensitive marker of oligodendrocyte maturation, we determined the S-MAG/L-MAG mRNA ratio by RT-PCR. These two MAG variants are produced by alternative splicing and their ratio increases during oligodendrocyte differentiation (Fujita et al, 1998). No significant differences in the S-MAG/L-MAG ratio at P10 or P28 were detected between the three genotypes examined (Fig.…”

Section: Normal Oligodendrocyte Differentiation In Fa2hmentioning

confidence: 87%

Absence of 2-Hydroxylated Sphingolipids Is Compatible with Normal Neural Development But Causes Late-Onset Axon and Myelin Sheath Degeneration

Zöller¹,

Meixner²,

Hartmann³

et al. 2008

J. Neurosci.

159

134

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Sphingolipids containing 2-hydroxylated fatty acids are among the most abundant lipid components of the myelin sheath and therefore are thought to play an important role in formation and function of myelin. To prove this hypothesis, we generated mice lacking a functional fatty acid 2-hydroxylase (FA2H) gene. FA2H-deficient (FA2H Ϫ/Ϫ ) mice lacked 2-hydroxylated sphingolipids in the brain and in peripheral nerves. In contrast, nonhydroxylated galactosylceramide was increased in FA2H Ϫ/Ϫ mice. However, oligodendrocyte differentiation examined by in situ hybridization with cRNA probes for proteolipid protein and PDGF␣ receptor and the time course of myelin formation were not altered in FA2H Ϫ/Ϫ mice compared with wild-type littermates. Nerve conduction velocity measurements of sciatic nerves revealed no significant differences between FA2H Ϫ/Ϫ and wild-type mice. Moreover, myelin of FA2H Ϫ/Ϫ mice up to 5 months of age appeared normal at the ultrastructural level, in the CNS and peripheral nervous system. Myelin thickness and g-ratios were normal in FA2H Ϫ/Ϫ mice. Aged (18-month-old) FA2H Ϫ/Ϫ mice, however, exhibited scattered axonal and myelin sheath degeneration in the spinal cord and an even more pronounced loss of stainability of myelin sheaths in sciatic nerves. These results show that structurally and functionally normal myelin can be formed in the absence of 2-hydroxylated sphingolipids but that its long-term maintenance is strikingly impaired. Because axon degeneration appear to start rather early with respect to myelin degenerations, these lipids might be required for glial support of axon function.

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“…The processes of central and peripheral axonal myelination are accomplished by partially distinct mechanisms Fujita et al, 1998). The myelinating cells of the CNS and PNS are distinct, with each oligodendrocyte myelinating multiple axonal internodes in the CNS, but Schwann cells providing myelination for a single peripheral axonal internode.…”

Section: Central Vs Peripheral Myelinationmentioning

confidence: 99%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,230

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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The Cytoplasmic Domain of the Large Myelin-Associated Glycoprotein Isoform Is Needed for Proper CNS But Not Peripheral Nervous System Myelination

Cited by 73 publications

References 51 publications

Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury

Genetic Deletion of Paired Immunoglobulin-Like Receptor B Does Not Promote Axonal Plasticity or Functional Recovery after Traumatic Brain Injury

Absence of 2-Hydroxylated Sphingolipids Is Compatible with Normal Neural Development But Causes Late-Onset Axon and Myelin Sheath Degeneration

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

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