Suppressing N-acetyl-l-aspartate synthesis prevents loss of neurons in a murine model of Canavan leukodystrophy

Jiho Sohn, Peter Bannerman, Fuzheng Guo, Travis Burns, Laird Miers, Christopher Croteau, Naveen K. Singhal, Jennifer A. McDonough, David E Pleasure

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Canavan disease is a leukodystrophy caused by aspartoacylase (ASPA) deficiency. The lack of functional ASPA, an enzyme enriched in oligodendroglia that cleaves N-acetyl-L-aspartate (NAA) to acetate and L-aspartic acid, elevates brain NAA and causes “spongiform” vacuolation of superficial brain white matter and neighboring gray matter. In children with Canavan disease, neuroimaging shows early-onset dysmyelination and progressive brain atrophy. Neuron loss has been documented at autopsy in some cases. Prior studies have shown that mice homozygous for the Aspa nonsense mutation Nur7 also develop brain vacuolation. We now report that numbers of cerebral cortical and cerebellar neurons are decreased and that cerebral cortex progressively thins in AspaNur7/Nur7 mice. This neuronal pathology is prevented by constitutive disruption of Nat8l, which encodes the neuronal NAA-synthetic enzyme N-acetyltransferase-8-like.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalJournal of Neuroscience
Volume37
Issue number2
DOIs
StatePublished - Jan 11 2017

Fingerprint

Canavan Disease
Neurons
Brain
Acetyltransferases
Nonsense Codon
Oligodendroglia
Enzymes
Aspartic Acid
Neuroimaging
Cerebral Cortex
Atrophy
Autopsy
Acetates
Pathology
N-acetylaspartate

Keywords

  • Aspartoacylase
  • Canavan disease
  • Myelin
  • N-acetyl-l-aspartate
  • N-acetyltransferase-8-like
  • Neuron

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Suppressing N-acetyl-l-aspartate synthesis prevents loss of neurons in a murine model of Canavan leukodystrophy. / Sohn, Jiho; Bannerman, Peter; Guo, Fuzheng; Burns, Travis; Miers, Laird; Croteau, Christopher; Singhal, Naveen K.; McDonough, Jennifer A.; Pleasure, David E.

In: Journal of Neuroscience, Vol. 37, No. 2, 11.01.2017, p. 413-421.

Research output: Contribution to journalArticle

Sohn, Jiho ; Bannerman, Peter ; Guo, Fuzheng ; Burns, Travis ; Miers, Laird ; Croteau, Christopher ; Singhal, Naveen K. ; McDonough, Jennifer A. ; Pleasure, David E. / Suppressing N-acetyl-l-aspartate synthesis prevents loss of neurons in a murine model of Canavan leukodystrophy. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 2. pp. 413-421.
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