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Apoptotic and necrotic cell death following kindling induced seizures
S Pretel1, C D Applegate, D Piekut
1Department of Neurobiology and Anatomy, School of Medicine and Dentistry, Rochester, N.Y. 14641, USA.
Abstract:
The study was designed to determine which type of cell death occurs following kindling induced seizures, and to determine which neurons die. For this purpose seizures were kindled from the entorhinal cortex. Following a range of 5-85 stage 5 seizures, rats were sacrificed, and the tissue was prepared for analysis. The TUNEL and silver impregnation methods were used to identify apoptotic or necrotic cell death, respectively. These methods were subsequently combined with immunocytochemistry, to determine if diseased neurons expressed somatostatin or the NMDA receptor (NMDAR1). The tissue analysis demonstrated that following kindling induced seizures, 1) hippocampal and extrahippocampal neurons die, 2) some neurons die through apoptosis, others through necrosis, and 3) some of the diseased neurons express somatostatin, others the NMDAR1 and that both subpopulations of neurons are present at hippocampal and extrahippocampal sites.
Insights
Kindling-induced seizures cause both hippocampal and extrahippocampal neuron death via apoptosis and necrosis. Diseased neurons express somatostatin or the NMDA receptor (NMDAR1).
Area of Science:
- Neuroscience
- Cell Biology
- Epilepsy Research
Background:
- Epilepsy is characterized by recurrent seizures, which can lead to neuronal damage.
- The specific mechanisms and cell types affected by kindling-induced seizures require further elucidation.
Purpose of the Study:
- To investigate the types of cell death (apoptosis vs. necrosis) occurring in neurons after kindling-induced seizures.
- To identify which specific neuronal populations undergo cell death and their molecular markers.
Main Methods:
- Seizures were induced in rats via kindling from the entorhinal cortex.
- TUNEL and silver impregnation techniques were employed to differentiate apoptotic and necrotic cell death.
- Immunocytochemistry was used to detect somatostatin and NMDA receptor (NMDAR1) expression in affected neurons.
Main Results:
- Kindling-induced seizures resulted in the death of both hippocampal and extrahippocampal neurons.
- Both apoptotic and necrotic cell death pathways were observed in the diseased neurons.
- A subset of dying neurons expressed somatostatin, while others expressed the NMDAR1, with both types found in hippocampal and extrahippocampal regions.
Conclusions:
- Kindling-induced seizures trigger diverse neuronal death mechanisms and affect widespread neuronal populations.
- The expression of somatostatin and NMDAR1 in dying neurons suggests their involvement in seizure-related pathology.
- Understanding these cell death pathways and neuronal markers is crucial for developing targeted epilepsy therapies.