[Abstract Title]. - Society for Neuroscience

failure to gain weight in young rats and weight loss in aged rats. However, in the previous study,
we could not determine an underlying biological mechanism for the weight loss effect in
hypothalamus. We hypothesized therefore that since the nigrostriatal tract passes through the
lateral hypothalamus, increased activity mediated by nigrostriatal DA may have been responsible
for the observed effect on body weight. In this study we compared bilateral injections of rAAV-
GDNF in hypothalamus versus substantia nigra in aged Brown Norway X Fischer 344 rats.
Nigrostriatal GDNF over-expression resulted in significantly greater weight loss than rats treated
in hypothalamus. The nigral or hypothalamic GDNF-induced weight loss was unrelated to food
intake or activity levels of the rats. Moreover, hypothalamic or striatal catecholamine levels did
not account for the observed effects on body weight. In contrast, significant DA increases in
nucleus accumbens was observed when GDNF was over-expressed either in hypothalamus or
SN. However, GDNF-induced increases in accumbens DA levels were larger in the
hypothalamic-treated group than in the SN treated group. Therefore, while increased accumbens
DA may partially account for the observed weight loss, increased DA cannot completely account
for the robust weight loss observed when GDNF is over-expressed in the nigrostriatal tract.
Disclosures: F.P. Manfredson, None; R.J. Mandel, None; K.R. Nash , None; N. Tumer,
None; P.J. Scarpace, None; B. Erdos, None; C.S. Broxson, None; L.F. Sullivan, None; T.
Landa, None; Y. Zhang, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.3/R10
Topic: C.02.d. Therapies
Support: NIH grant NS052733
Title: The antiepileptic drug zonisamide protects in MPTP model of Parkinson's disease
Authors: *P. K. SONSALLA, L.-Y. WONG;
Dept of Neurol, UMDNJ RW Johnson Med. Sch., Piscataway, NJ
Abstract: Parkinson‟s disease (PD) is a debilitating progressive neurodegenerative disorder in
which loss of motor function results from the degeneration of nigrostriatal dopamine (DA)
neurons. There is at present no cure for PD. Zonisamide is an FDA-approved antiepileptic drug
that has neuroprotective actions against hippocampal neuronal damage in seizure models.
Moreover, in a randomized clinical study, zonisamide improved motor function in PD patients
possibly due to its ability to increase DA release. Preliminary reports by others suggest that