[Abstract Title]. - Society for Neuroscience

Abstract: Ghrelin targets the hypothalamus to regulate food intake and adiposity. Endogenous
ghrelin receptors (growth hormone secretagogue receptor, GHSR) are also present in
extrahypothalamic sites where they promote circuit activity associated with learning and
memory, and reward seeking behavior. Here, we show that the substantia nigra pars compacta
(SNpc), a brain region where dopamine (DA) cell degeneration leads to Parkinson‟s disease
(PD), expresses GHSR. Ghrelin binds to SNpc cells, electrically activates SNpc DA neurons,
increases midbrain mitochondrial respiratory capacity, tyrosine hydroxylase mRNA and
increases DA concentration in the dorsal striatum. Exogenous ghrelin administration for 14 days
to mice decreased SNpc DA cell loss and diminished striatal dopamine levels after 1-methyl-4phenyl-1,2,5,6
tetrahydropyridine (MPTP) treatment. Genetic ablation of ghrelin increased SNpc
DA cell loss and lowered striatal dopamine levels after MPTP treatment. Ghrelin-induced
neuroprotection was mediated by enhanced uncoupling protein 2 (UCP2)-dependent
mitochondrial function and biogenesis. Exogenous ghrelin administration for 14 days to UCP2
knockout mice did not rescue SNpc TH cell loss in MPTP treated mice, as observed in UCP2
wild type. Taken together, our data reveals that ghrelin plays an important role in the
maintenance and protection of normal nigrostriatal dopamine function thereby offering a novel
therapeutic strategy to combat neurodegeneration associated with PD.
Disclosures: Z.B. Andrews, None; T.L. Horvath, None; R. Roth, None; J. Elsworth, None; D.
Erion, None; R. Beiler, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.6/S1
Topic: C.02.d. Therapies
Support: Swedish Brain Foundation
Swedish Research Council
Swedish Brain Power
Swedish Parkinson Foundation
Title: A2A receptor antagonist treatment counteract symptoms in the MitoPark mouse model of
progressive Parkinson‟s disease