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Bcl-2 and its homologues in the brain of patients with multiple sclerosis
Ileana Banisor1, Bernadette Kalman
1Department of Neurology, SLRHC, Hospital of Columbia University, New York 10019, USA. BKalman@chpnet.org
Abstract:
We measured the mRNA expression levels of molecules involved in scavenging free radicals and in apoptosis within normal appearing white and gray matter (NAWM and NAGM, respectively) and chronic active plaque containing frontal lobe specimens of patients with multiple sclerosis (MS). While no regional differences were detected in the mRNA levels of free radical scavengers, Bcl-XL was higher in plaques than in NAWMs, and both Bak and Bcl-2 were found to be increased in correlation with an immune marker (beta2-microglobulin--beta2Mg) in NAWM and plaque compared with corresponding cortical regions. We did not measure a similar white-gray matter difference in the expression of the latter genes in brains of normal or Alzheimer disease controls. This finding indicates that both pro- and anti-apoptotic mechanisms are activated, not only within but also outside of plaques.
Insights
In multiple sclerosis (MS), both pro- and anti-apoptotic mechanisms are active within and outside of lesions. Bcl-XL was elevated in plaques, while Bak and Bcl-2 correlated with immune markers in normal-appearing and plaque tissues.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Multiple sclerosis (MS) involves inflammation and neurodegeneration.
- Apoptosis (programmed cell death) and free radical damage are implicated in MS pathology.
- Understanding molecular changes in different brain regions is crucial for MS research.
Purpose of the Study:
- To investigate mRNA expression of apoptosis-related and free radical scavenging molecules in MS brain tissue.
- To compare these expression levels between chronic active plaques, normal-appearing white matter (NAWM), and normal-appearing gray matter (NAGM).
- To explore correlations between apoptotic markers and immune markers in MS brains.
Main Methods:
- Quantitative analysis of mRNA expression levels.
- Target genes included free radical scavengers and apoptosis regulators (e.g., Bcl-XL, Bak, Bcl-2).
- Brain tissue specimens from MS patients, normal controls, and Alzheimer's disease patients were analyzed.
Main Results:
- No significant regional differences in free radical scavenger mRNA levels were found.
- Bcl-XL mRNA levels were higher in active MS plaques compared to NAWM.
- Bak and Bcl-2 mRNA levels increased in correlation with beta-2-microglobulin (an immune marker) in both NAWM and plaques.
Conclusions:
- Both pro-apoptotic (Bak) and anti-apoptotic (Bcl-2, Bcl-XL) mechanisms are activated in MS brain tissue.
- These apoptotic processes occur both within active plaques and in surrounding normal-appearing white and gray matter.
- The findings suggest a complex interplay of apoptotic and immune responses in MS pathogenesis, extending beyond focal lesions.
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