Δ9-tetrahydrocannabinol (Δ9-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease.
Neuropathol Appl Neurobiol
; 38(6): 535-47, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22236282
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Dronabinol
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Fármacos Neuroprotectores
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Receptor Cannabinoide CB1
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Neuronas
Límite:
Humans
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido