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Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease.
Neuropathol Appl Neurobiol. 2012 Oct; 38(6):535-47.NA

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.

Authors+Show Affiliations

Department of Clinical Neurobiology, Peninsula College of Medicine and Dentistry, University of Plymouth, Plymouth, UK. camille.carroll@pms.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22236282

Citation

Carroll, C B., et al. "Δ⁹-tetrahydrocannabinol (Δ⁹-THC) Exerts a Direct Neuroprotective Effect in a Human Cell Culture Model of Parkinson's Disease." Neuropathology and Applied Neurobiology, vol. 38, no. 6, 2012, pp. 535-47.
Carroll CB, Zeissler ML, Hanemann CO, et al. Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease. Neuropathol Appl Neurobiol. 2012;38(6):535-47.
Carroll, C. B., Zeissler, M. L., Hanemann, C. O., & Zajicek, J. P. (2012). Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease. Neuropathology and Applied Neurobiology, 38(6), 535-47. https://doi.org/10.1111/j.1365-2990.2011.01248.x
Carroll CB, et al. Δ⁹-tetrahydrocannabinol (Δ⁹-THC) Exerts a Direct Neuroprotective Effect in a Human Cell Culture Model of Parkinson's Disease. Neuropathol Appl Neurobiol. 2012;38(6):535-47. PubMed PMID: 22236282.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Δ⁹-tetrahydrocannabinol (Δ⁹-THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease. AU - Carroll,C B, AU - Zeissler,M-L, AU - Hanemann,C O, AU - Zajicek,J P, PY - 2012/1/13/entrez PY - 2012/1/13/pubmed PY - 2013/2/23/medline SP - 535 EP - 47 JF - Neuropathology and applied neurobiology JO - Neuropathol Appl Neurobiol VL - 38 IS - 6 N2 - 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. SN - 1365-2990 UR - https://www.unboundmedicine.com/medline/citation/22236282/Δ⁹_tetrahydrocannabinol__Δ⁹_THC__exerts_a_direct_neuroprotective_effect_in_a_human_cell_culture_model_of_Parkinson's_disease_ L2 - https://doi.org/10.1111/j.1365-2990.2011.01248.x DB - PRIME DP - Unbound Medicine ER -