Δ 9 -tetrahydrocannabinol (Δ 9 -THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease

Department of Clinical Neurobiology, Peninsula College of Medicine and Dentistry, University of Plymouth, Plymouth, UK.
Neuropathology and Applied Neurobiology (Impact Factor: 3.93). 01/2012; 38(6):535-47. DOI: 10.1111/j.1365-2990.2011.01248.x
Source: PubMed


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.

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    • "The benefit of cannabinoids in PD is not limited to the symptomatic amelioration. Lately, several reports have revealed interesting neuroprotective and anti-inflammatory effects of these drugs in cell cultures and animal models of PD (Lastres-Becker et al., 2005; Garcia-Arencibia et al., 2007; Fernandez-Ruiz et al., 2011; Jeon et al., 2011; Carroll et al., 2012). Although CB1 receptor-mediated effects cannot be excluded, some authors argue that CB1 receptors may have a minimal implication in neuroprotection (Lastres-Becker et al., 2005; Fernandez-Ruiz et al., 2007; Price et al., 2009; Chung et al., 2011). "
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