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White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

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Abstract
In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in beta(2) adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies.
Keywords
OXIDE SYNTHASE EXPRESSION, multiple sclerosis, CEREBROSPINAL-FLUID, axonal degeneration, RAT-BRAIN, CREATINE-KINASE-BB, GLUTAMATE TRANSPORTERS, N-ACETYLASPARTATE, URIC-ACID, IN-VIVO, MAGNETIC-RESONANCE-SPECTROSCOPY, energy metabolism, SPINAL-CORD, astrocytes

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Chicago
Cambron, Melissa, Miguel D’haeseleer, Guy Laureys, Ralph Clinckers, Jan Debruyne, and Jacques De Keyser. 2012. “White-matter Astrocytes, Axonal Energy Metabolism, and Axonal Degeneration in Multiple Sclerosis.” Journal of Cerebral Blood Flow and Metabolism 32 (3): 413–424.
APA
Cambron, M., D’haeseleer, M., Laureys, G., Clinckers, R., Debruyne, J., & De Keyser, J. (2012). White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 32(3), 413–424.
Vancouver
1.
Cambron M, D’haeseleer M, Laureys G, Clinckers R, Debruyne J, De Keyser J. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM. 2012;32(3):413–24.
MLA
Cambron, Melissa, Miguel D’haeseleer, Guy Laureys, et al. “White-matter Astrocytes, Axonal Energy Metabolism, and Axonal Degeneration in Multiple Sclerosis.” JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM 32.3 (2012): 413–424. Print.
@article{4183726,
  abstract     = {In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which may impair the astrocytic sodium potassium pump and lead to a reduced sodium-dependent glutamate uptake. Astrocytes in MS white matter appear to be deficient in beta(2) adrenergic receptors, which are involved in stimulating glycogenolysis and suppressing inducible nitric oxide synthase (NOS2). Glutamate toxicity, reduced astrocytic glycogenolysis leading to reduced lactate and glutamine production, and enhanced nitric oxide (NO) levels may all impair axonal mitochondrial metabolism, leading to axonal degeneration. In addition, glutamate-mediated oligodendrocyte damage and impaired myelination caused by a decreased production of N-acetylaspartate by axonal mitochondria might also contribute to axonal loss. White-matter astrocytes may be considered as a potential target for neuroprotective MS therapies.},
  author       = {Cambron, Melissa and D'haeseleer, Miguel and Laureys, Guy and Clinckers, Ralph and Debruyne, Jan and De Keyser, Jacques},
  issn         = {0271-678X},
  journal      = {JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM},
  keywords     = {OXIDE SYNTHASE EXPRESSION,multiple sclerosis,CEREBROSPINAL-FLUID,axonal degeneration,RAT-BRAIN,CREATINE-KINASE-BB,GLUTAMATE TRANSPORTERS,N-ACETYLASPARTATE,URIC-ACID,IN-VIVO,MAGNETIC-RESONANCE-SPECTROSCOPY,energy metabolism,SPINAL-CORD,astrocytes},
  language     = {eng},
  number       = {3},
  pages        = {413--424},
  title        = {White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis},
  url          = {http://dx.doi.org/10.1038/jcbfm.2011.193},
  volume       = {32},
  year         = {2012},
}

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