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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 490-9 |
| Number of pages | 10 |
| Journal | Archives of Neurology |
| Volume | 69 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2012 |
Keywords / Materials (for Non-textual outputs)
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antigens, CD
- Antigens, Differentiation, Myelomonocytic
- Autopsy
- Basic Helix-Loop-Helix Transcription Factors
- Case-Control Studies
- DNA Mutational Analysis
- DNA, Mitochondrial
- Electron Transport Complex IV
- Female
- Gene Deletion
- Gene Expression Regulation
- Humans
- Kearns-Sayre Syndrome
- Male
- Middle Aged
- Mitochondria
- Myelin Basic Protein
- Myelin Sheath
- Myelin-Associated Glycoprotein
- Nerve Degeneration
- Nerve Tissue Proteins
- Retrospective Studies
- Succinate Dehydrogenase
- Synaptophysin
- Young Adult