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Decreased hippocampal expression of calbindin D28K and cognitive impairment in MELAS
Valentina Emmanuele1, Angels Garcia-Cazorla, Hua-Bin Huang
1Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
Abstract:
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial syndrome characterized by seizures, migrainous headaches, lactic acidosis, vomiting, and recurrent stroke-like episodes. Patients often suffer from cognitive dysfunction of unclear pathogenesis. In this study, we explored a possible link between cognitive dysfunction and hippocampal expression of calbindin D(28KD) (CB), a high affinity calcium-binding protein, in four MELAS patients, using post mortem hippocampal tissues. We found significantly reduced CB levels in all patients by immunohistochemistry, Western blot, and quantitative real-time PCR. Reduction in CB expression has been associated with aging and with neurodegenerative disorders, including Alzheimer's disease. We postulate that the reduced CB expression may play a role in the cognitive abnormalities associated with MELAS.
Insights
Cognitive dysfunction in MELAS patients may stem from reduced calbindin D(28KD) (CB) levels in the hippocampus. This study found significantly lower CB expression in post-mortem brain tissues from MELAS individuals.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Genetics
Background:
- Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited disorder.
- Patients with MELAS frequently experience cognitive dysfunction, but its underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate the potential association between cognitive impairment and hippocampal expression of calbindin D(28KD) (CB) in MELAS patients.
- To explore the role of CB, a calcium-binding protein, in the pathogenesis of cognitive deficits in MELAS.
Main Methods:
- Analysis of post-mortem hippocampal tissues from four MELAS patients.
- Utilized immunohistochemistry, Western blot, and quantitative real-time PCR to assess CB levels.
- Compared CB expression in MELAS patients to established associations with aging and neurodegenerative diseases.
Main Results:
- Significantly reduced levels of calbindin D(28KD) (CB) were observed in the hippocampi of all MELAS patients studied.
- Immunohistochemistry, Western blot, and qPCR confirmed the diminished CB expression.
- Reduced CB expression is a known factor in aging and neurodegenerative conditions like Alzheimer's disease.
Conclusions:
- The study suggests a potential link between reduced hippocampal CB expression and cognitive dysfunction in MELAS.
- Diminished CB levels may contribute to the neurological abnormalities observed in MELAS patients.
- Further research is warranted to elucidate the precise role of CB in MELAS-associated cognitive decline.
