RT Journal Article SR Electronic T1 108 Investigating the neuroprotective properties of Δ9-THC in a cell culture model of Parkinson's disease JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP e1 OP e1 DO 10.1136/jnnp-2011-301993.150 VO 83 IS 3 A1 M Zeissler A1 C B Carroll A1 C O Hanemann A1 J P Zajieck YR 2012 UL http://jnnp.bmj.com/content/83/3/e1.58.abstract AB Background Δ9-tetrahydrocannabinol (Δ9-THC) is neuroprotective in models of Parkinson's disease (PD). Although CB1 receptors are increased within the basal ganglia of PD patients and animal models, current evidence suggests a role for CB1 receptor independent mechanisms such as anti-oxidant activity. Here we investigate the mechanisms behind the neuroprotective potential of Δ9-THC in a human cell culture model of PD.Methods SH-SY5Y neuroblastoma cells were differentiated with retinoic acid and exposed to the PD relevant neurotoxin MPP+. Cannabinoids and modulatory compounds were co-administered with MPP+ for 48 h after which cell death was determined using the LDH assay. Protein levels of PPARγ were determined by western blotting.Results The protective effect of Δ9-THC was not blocked by the CB1 antagonist AM251, nor reproduced by the CB1 agonist WIN55, 212-2. The anti-oxidants α-tocopherol and butylhydroxytoluene were unable to elicit the same neuroprotection as Δ9-THC. The antioxidant Δ9-THC analogue nabilone potentiated neurotoxicity induced by MPP+. Co-application of the specific PPARγ agonist pioglitazone was protective against MPP+ toxicity and the PPARγ antagonist T0070907 dose dependently blocked the neuroprotective effect of Δ9-THC. Δ9-THC increased PPARγ expression indicating PPARγ activation.Conclusions We propose that the neuroprotective effect of Δ9-THC may be mediated by PPARγ activation rather than via the CB1 receptor or its antioxidant properties.