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Is the cell death in mesial temporal sclerosis apoptotic?
Hilmi Uysal1, Isin Unal Cevik, Figen Soylemezoglu
1Department of Neurology, Sevgi Hospital, Hacettepe University Hospitals, Ankara, Turkey.
Purpose:
Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures.
Methods:
We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 +/- 8 years).
Results:
Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in approximately 10% of these neurons. Despite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining.
Conclusions:
These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility.
Insights
Apoptosis may contribute to neuronal loss in mesial temporal sclerosis (MTS) in epilepsy patients. While DNA fragmentation wasn't detected, increased Bax and caspase activity suggest slow apoptotic cell death in MTS.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Mesial temporal sclerosis (MTS) involves hippocampal neuronal loss, often linked to intractable epilepsy.
- Recurrent seizures in epilepsy may trigger neuronal death via apoptosis.
Purpose of the Study:
- To investigate evidence of apoptotic cell death in temporal lobes of drug-resistant epilepsy patients with MTS.
- To examine the expression of apoptosis-related proteins (Bcl-2, Bax, fractin) and DNA fragmentation.
Main Methods:
- Analysis of 15 temporal lobe resections from MTS patients using TUNEL assay and immunohistochemistry.
- Detection of Bcl-2, Bax, and caspase-cleaved actin fragment (fractin) expression.
Main Results:
- Increased Bax immunopositivity and fractin staining (indicating caspase activity) were observed in hippocampal neurons.
- Bcl-2 was found in remaining neurons and astroglia.
- No DNA fragmentation (TUNEL assay) or typical apoptotic nuclear morphology was detected.
Conclusions:
- Apoptosis's role in MTS cell loss remains uncertain; slow cell death may hinder detection.
- Elevated Bax expression and caspase activation suggest apoptosis might occur slowly in MTS.
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