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Abstracts from the Association of British Neurologists Annual Meeting 2011
108 Investigating the neuroprotective properties of Δ9-THC in a cell culture model of Parkinson's disease
  1. M Zeissler,
  2. C B Carroll,
  3. C O Hanemann,
  4. J P Zajieck
  1. Peninsula College of Medicine and Dentistry

Abstract

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.

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Footnotes

  • Email: camille.carroll{at}pms.ac.uk

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