Date of Award

2003

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Linda Friedman

Committee Member

Allan Blake

Committee Member

Sulie Chang

Keywords

Proto-oncogenes, Epilepsy, Developmental epilepsy, Seizures

Abstract

Seizures cause selective neuronal cell loss in vulnerable regions such as the hippocampus, cortex, thalamus or substantia nigra (SN) in human or experimental animals. While the HF can propagate seizures, the SN pars reticulata (SNR) regulates the spread ol seizures in an age-dependent fashion, and the pars compacta (SNC) affects extrapyramidal motor control. In mature animals, both structures are wlnerable to seizure-induced damage. In prepubescent rats, seizure susceptibility is reduced and CA 1 region rs primarily affected. The proto-oncogenes, Bcl-2 and Bax, encode specific proteins that inhibit and promote programmed cell death, respectively. In order to determine whether proto-oncogenes are involved in cell death or survival, we examined mRNA and protein expression of Bax and Bcl-2 during several maturational I (P13, P20, P30) stages. We used in silu hybridization and immunohistochemistry following a single episode of KA-induced status epilepticus. At P13, there was no apparent change in the expression levels of Bax or Bcl-2 mRNA or protein within the hippocampus, 48h after status epilepticus. In contrast, Bcl-2 proteins markedly declined within the SN sub- regions at P20 and P30, stages lhal do not exhibit SN damage at the times examined. Similar observations were found in the hippocampus at P20 and P30, except that their expression decreased in areas of cell injury or neuronal loss. Adjacent sections showed that tyrosine hydroxylase (TH) and glutamic acid decarboxylase GAD levels were undisturbed in the SN. These result suggest that proto-oncogene regulation is not always associated with cell death or survival. Instead, changes in oncogenes expression may regulate the function of major neurotransmitters that provide homeostatic balance between excitation and inhibition, or inhibition of these oncogenes may play a critical role in the age-specific effects that the SNR and selective midbraln nuclei have on seizures.

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