[Abstract Title]. - Society for Neuroscience

zonisamide 1) elevates the brain content of glutathione, an important brain antioxidant, 2)
provides neuroprotection against 6-hydroxydopamine, and 3) modifies DA neurotransmission.
Based on these observations, we hypothesized that zonisamide would protect against MPTPinduced
damage to DA neurons. Mice were treated once daily for 3 days with MPTP (30, 30 and
15 mg/kg, sc). Mice receiving zonisamide (20 mg/kg, ip) were pretreated 15 min before each
MPTP administration. Mice were killed 7 days after the last treatment. MPTP treatment
produced a profound lesioning of striatal DA nerve terminals as evidenced by 84 ± 6% and 92 ±
4% reductions in tyrosine hydroxylase (TH) and DA, respectively. In mice treated with
zonisamide and MPTP, the reductions in TH and DA were only 21 ± 11% and 50 ± 13%,
respectively, and were statistically different from MPTP-only treatment. DA and TH content
were not altered in mice treated with zonisamide alone. The IC50 for zonisamide inhibition of
MAO B was ~300 uM. Moreover, in ex vivo studies, zonisamide treatment of mice did not
interfere with the irreversible binding of systemically administered deprenyl to MAO B.
Zonisamide does not interfere with DA uptake into synaptosomes (Okada et al. Epilepsy Res,
22:193-205, 1995). Thus, zonisamide does not appear to alter pharmacokinetic or
pharmacodynamic properties of MPTP/MPP+ although experiments will be conducted to
measure the actual striatal content of MPP+ in both groups of mice. The mechanism(s) by which
zonisamide protects as well as whether it protects in chronic PD models remains to be
established. However, the finding that a drug which is already used clinically might retard DA
neurodegeneration in PD is very encouraging. If additional pre-clinical studies in other PD
models confirm the neuroprotective effect of zonisamide, they would pave the way for clinical
trials examining the neuroprotective properties of zonisamide in PD patients. Supported by NIH
NS052733.
Disclosures: P.K. Sonsalla, None; L. Wong, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.4/R11
Topic: C.02.d. Therapies
Support: Fondation de France (032153-2005013853)
Title: Consequences of chronic subthalamic nucleus high-frequency stimulation on striatal
activity in intact and parkinsonian rats: in vitro and in vivo recordings
Authors: P. GUBELLINI 1 , S. LARDEUX 2 , *P. P. SALIN 3 , D. PALERESSOMPOULLE 2 , C.
BAUNEZ 2 ;