[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 253.1/X2
Abstract: Withdrawn
Poster
253. Parkinson's Disease Models: Neuroprotective Mechanisms I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 253.2/X3
Topic: C.11.j. Neuroprotective mechanisms: Parkinson‟s disease models
Support: F. M. Kirby Foundation
Title: The neuroprotective potential of taurine and dextromethorphan in acute and subacute
MPTP-treated mice
Authors: *D. W. ANDERSON 1 , J. S. SCHNEIDER 2 ;
1 Dept Pathol, Anat & Cell Biol, 2 Pathology, Anat. and Cell Biol., Thomas Jefferson Univ.,
Philadelphia, PA
Abstract: No single factor has been identified as the primary cause of dopamine (DA) neuron
death in the substantia nigra pars compacta (SNc) in idiopathic Parkinson‟s disease (PD).
However, both mitochondrial dysfunction and oxidative stress may play important roles in the
pathogenesis of PD, with postmortem studies suggesting complex 1 defects in PD patients and
animal studies showing DA neuron degeneration from oxidative stress and oxidizing toxins.
There is also no consensus as to the mode of DA neuron death in PD, with some postmortem
studies of PD brains detecting signs of apoptosis in the SNc while others have found no evidence
of apoptosis. Additionally, there are some shortcomings in the way animal models of PD have
been utilized in the search for neuroprotective therapies. We have previously shown that the
efficacy of putative neuroprotective agents can vary greatly depending upon the way in which
the toxin MPTP is administered to mice (i.e., acute vs. sub-acute administration) and the type of
cell death that is produced (necrotic vs. apoptotic). The complexity of cell death in PD and the
way in which animal models have been utilized to date (mostly relying on acute MPTP
administration) likely underlie the disappointing results in the clinic in the search for an effective
neuroprotective agent. The current study assessed the efficacy of two putative neuroprotective
agents with glutamatergic actions, taurine and dextromethorphan (DM), on DA cell survival in
two MPTP models. Taurine is a sulfonated amino acid found in high concentration in many brain
regions that, among a variety of other physiological functions, can presynaptically attenuate