Details

Autor(en) / Beteiligte

• Carroll, C. B.
• Zeissler, M.-L.
• Hanemann, C. O.
• Zajicek, J. P.

Titel

Δ9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease

Ist Teil von

• Neuropathology and applied neurobiology, 2012-10, Vol.38 (6), p.535-547

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2012

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• C. B. Carroll, M.‐L. Zeissler, C. O. Hanemann and J. P. Zajicek (2012) Neuropathology and Applied Neurobiology38, 535–547 Δ9‐tetrahydrocannabinol (Δ9‐THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease Aims: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. Here, we utilized a human neuronal cell culture PD model to further investigate the protective properties of Δ9‐THC. Methods: Differentiated SH‐SY5Y neuroblastoma cells were exposed to PD‐relevant toxins: 1‐methyl‐4‐phenylpyridinium (MPP+), lactacystin and paraquat. Changes in CB1 receptor level were determined by quantitative polymerase chain reaction and Western blotting. Cannabinoids and modulatory compounds were co‐administered with toxins for 48 h and the effects on cell death, viability, apoptosis and oxidative stress assessed. Results: We found CB1 receptor up‐regulation in response to MPP+, lactacystin and paraquat and a protective effect of Δ9‐THC against all three toxins. This neuroprotective effect was not reproduced by the CB1 receptor agonist WIN55,212‐2 or blocked by the CB1 antagonist AM251. Furthermore, the antioxidants α‐tocopherol and butylhydroxytoluene as well as the antioxidant cannabinoids, nabilone and cannabidiol were unable to elicit the same neuroprotection as Δ9‐THC. However, the peroxisome proliferator‐activated receptor‐gamma (PPARγ) antagonist T0070907 dose‐dependently blocked the neuroprotective, antioxidant and anti‐apoptotic effects of Δ9‐THC, while the PPARγ agonist pioglitazone resulted in protection from MPP+‐induced neurotoxicity. Furthermore, Δ9‐THC increased PPARγ expression in MPP+‐treated SH‐SY5Y cells, another indicator of PPARγ activation. Conclusions: We have demonstrated up‐regulation of the CB1 receptor in direct response to neuronal injury in a human PD cell culture model, and a direct neuronal protective effect of Δ9‐THC that may be mediated through PPARγ activation.