Loss of myelin-associated glycoprotein in kearns-sayre syndrome.

Abstract

OBJECTIVE:

To explore myelin components and mitochondrial changes within the central nervous system in patients with well-characterized mitochondrial disorders due to nuclear DNA or mitochondrial DNA (mtDNA) mutations.

DESIGN:

Immunohistochemical analysis, histochemical analysis, mtDNA sequencing, and real-time and long-range polymerase chain reaction were used to determine the pathogenicity of mtDNA deletions.

SETTING:

Department of Clinical Pathology, Columbia University Medical Center, and Newcastle Brain Tissue Resource.

PATIENTS:

Seventeen patients with mitochondrial disorders and 7 controls were studied from August 1, 2009, to August 1, 2010.

MAIN OUTCOME MEASURE:

Regions of myelin-associated glycoprotein (MAG) loss.

RESULTS:

Myelin-associated glycoprotein loss in Kearns-Sayre syndrome was associated with oligodendrocyte loss and nuclear translocation of apoptosis-inducing factor, whereas inflammation, neuronal loss, and axonal injury were minimal. In a Kearns-Sayre syndrome MAG loss region, high levels of mtDNA deletions together with cytochrome- c oxidase-deficient cells and loss of mitochondrial respiratory chain subunits (more prominent in the white than gray matter and glia than axons) confirmed the pathogenicity of mtDNA deletions.

CONCLUSION:

Primary mitochondrial respiratory chain defects affecting the white matter, and unrelated to inflammation, are associated with MAG loss and central nervous system demyelination.

• Authors: Nichola Z Lax, Graham R Campbell, Amy K Reeve, Nobuhiko Ohno, Jessica Zambonin, Emma L Blakely, Robert W Taylor, Eduardo Bonilla, Kurenai Tanji, Salvatore DiMauro, Evelyn Jaros, Hans Lassmann, Doug M Turnbull, Don J Mahad
• Journal: Archives of neurology (Arch Neurol) Vol. 69 Issue 4 Pg. 490-9 (Apr 2012) ISSN: 1538-3687 [Electronic] United States
• PMID: 22491194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Basic Helix-Loop-Helix Transcription Factors
• CD68 antigen, human
• DNA, Mitochondrial
• Myelin Basic Protein
• Myelin-Associated Glycoprotein
• Nerve Tissue Proteins
• OLIG2 protein, human
• Oligodendrocyte Transcription Factor 2
• Synaptophysin
• Succinate Dehydrogenase
• Electron Transport Complex IV

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Autopsy
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Case-Control Studies
• DNA Mutational Analysis
• DNA, Mitochondrial (analysis, genetics)
• Electron Transport Complex IV (metabolism)
• Female
• Gene Deletion
• Gene Expression Regulation (genetics)
• Humans
• Kearns-Sayre Syndrome (complications, genetics, metabolism, pathology)
• Male
• Middle Aged
• Mitochondria (metabolism)
• Myelin Basic Protein (metabolism)
• Myelin Sheath (metabolism)
• Myelin-Associated Glycoprotein (genetics, metabolism)
• Nerve Degeneration (etiology, genetics)
• Nerve Tissue Proteins (metabolism)
• Oligodendrocyte Transcription Factor 2
• Retrospective Studies
• Succinate Dehydrogenase (metabolism)
• Synaptophysin (metabolism)
• Young Adult