Status Epilepticus Downregulates Bax and Bcl-2 Proteins in the Substantia Nigra of Prebubescent Rats.
Abstract number :
2.008
Submission category :
Year :
2001
Submission ID :
279
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
M. Shafiei, MS, Biology, NJ Neuroscience Institute, So Orange, NJ; L.K. Friedman, PhD, Neuroscience, NJ Neuroscience Institute, So Orange, NJ; B.W. Magrys, MA, Neuroscience, NJ Neuroscience Institute, So Orange, NJ; H. Liu, MD/PhD, Neuroscience, NJ Neuros
RATIONALE: While the hippocampus can propagate seizures, the substantia nigra pars reticulata (SNR) regulates the spread of seizures in an age-dependent fashion and the pars compacta (SNC) impacts on motor control. With maturation, both structures are vulnerable to seizure-induced damage. The proto-oncogenes, Bax and Bcl-2, encode specific proteins that either promote or inhibit programmed cell death, respectively. The pro-apoptotic BAX gene is activated following subcellular translocation and dimerization.
METHODS: To study whether the immature brain is resistant to seizure-induced cell death due to regulation of Bax or Bcl-2 proto-oncogenes, we examined by in situ hybridization and immunohistochemistry the expression of Bax and Bcl-2 at three postnatal (P) ages (P14, P20, and P30) following kainate-induced status epilepticus. Animals were sacrificed 24-72hrs after KA injection, times before and after the first appearance of hippocampal or extrahippocampal damage.
RESULTS: At P14 and at 48-72 hrs after status epilepticus, there was no apparent change in the expression of either mRNA or protein levels within the hippocampus or SN. At P20 or P30 and similar times after status epilepticus marked reductions in the expression of Bax protein occurred throughout the SN. Bcl-2 immunolabeling was also decreased but to a lesser degree. Adjacent sections showed tyrosine hydroxylase levels were undisturbed in SNC. Decreases in Bax but not Bcl-2 were also noted in the pararubral nucleus of the midbrain. Within the hippocampus, proliferating glial cells were marked with Bax antibodies. Histology showed the SN and pararubral nuclei were intact while the hippocampus, particularly the CA1, was highly injured. Decreases in hippocampal Bax and Bcl-2 proteins were associated with injury.
CONCLUSIONS: Therefore, the altered Bcl-2 and Bax protein patterns do not correlate with cell death or survival at ages examined. Instead, inhibition of these oncogenes may play a critical role in the age-specific effects that the SNR, SNC and selective midbrain nuclei have on seizures and execution of movement.