[Abstract Title]. - Society for Neuroscience

PUFA in PD mice although the underlying mechanisms of action remain to be elucidated. Here,
we exposed mice to either a control or a high n-3 PUFA diet from 2 to 12 months of age and then
treated them with MPTP (140 mg/kg in 5 days), neurotoxin that targets the dopaminergic
pathway. The high n-3 PUFA consumption modified the brain fatty acids profile. It also
completely prevented the MPTP-induced decrease of tyrosine hydroxylase (TH)-labeled nigral
cells (p < 0.01 versus MPTP mice on control diet), Nurr1 mRNA levels (p < 0.01 versus MPTP
mice on control diet) and dopamine transporter mRNA levels (p < 0.05 versus MPTP mice on
control diet) in the substantia nigra. Although n-3 PUFA dietary treatment had no effect on
striatal dopaminergic terminals, the high n-3 PUFA diet protected against the MPTP-induced
decrease in dopamine (p < 0.05 versus MPTP mice on control diet) and its metabolite
dihydroxyphenylacetic acid (DOPAC) (p < 0.05 versus MPTP mice on control diet) in the
striatum. Thus far, we have investigated three main mechanistic pathways involving: 1)
inflammation, 2) heat shock proteins and 3) neurotrophic factors. PK11195 binds to peripheral
benzodiazepine receptors on glial cells, which are upregulated during inflammatory response. As
assessed with autoradiography, the specific binding of [3H]-PK11195 remained unchanged in
mice fed the high n-3 PUFA diet. In situ hybridization revealed no differences in heat shock
protein (hsp70) mRNA levels between animals on either diet. However, we have detected a
higher expression of brain-derived neurotrophic factor (BDNF) mRNA in the cortex of mice fed
the high n-3 PUFA diet (p < 0.05 versus mice on control diet). In light of these preliminary
observations, we are now focusing mainly on mechanisms related to neurotrophic factors and
expression of their receptors that could underlie the neuroprotective action of n-3 PUFA
observed here. Regulation of oxidative damage is also being investigated. Since the prevalent
low consumption of n-3 PUFA might be an important modifiable risk factor of PD, our data call
for further investigation on the neuroprotective effect of n-3 PUFA in neurodegenerative
diseases.
Disclosures: M. Bousquet, None; M. Saint-Pierre, None; C. Julien, None; N. Salem, None; F.
Cicchetti, None; F. Calon, None.
Poster
253. Parkinson's Disease Models: Neuroprotective Mechanisms I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 253.13/X14
Topic: C.11.j. Neuroprotective mechanisms: Parkinson‟s disease models
Support: SEOULRNBD program(10524)
Title: Polygala radix protects dopaminergic cell from toxicity induced by MPTP in mice model
of Parkinson's disease