{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:35:11Z","timestamp":1790994911179,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,9,17]],"date-time":"2012-09-17T00:00:00Z","timestamp":1347840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p>C. B. Carroll, M.\u2010L. Zeissler, C. O. Hanemann and J. P. Zajicek (2012) <jats:italic>Neuropathology and Applied Neurobiology<\/jats:italic><jats:bold>38,<\/jats:bold> 535\u2013547<\/jats:p><jats:p><jats:bold>\u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (\u0394<jats:sup>9<\/jats:sup>\u2010THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease<\/jats:bold><\/jats:p><jats:p><jats:bold>Aims:<\/jats:bold>\u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (\u0394<jats:sup>9<\/jats:sup>\u2010THC) 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\u2010independent mechanisms. Here, we utilized a human neuronal cell culture PD model to further investigate the protective properties of \u0394<jats:sup>9<\/jats:sup>\u2010THC. <jats:bold>Methods:<\/jats:bold> Differentiated SH\u2010SY5Y neuroblastoma cells were exposed to PD\u2010relevant toxins: 1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>), lactacystin and paraquat. Changes in CB1 receptor level were determined by quantitative polymerase chain reaction and Western blotting. Cannabinoids and modulatory compounds were co\u2010administered with toxins for 48\u2003h and the effects on cell death, viability, apoptosis and oxidative stress assessed. <jats:bold>Results:<\/jats:bold> We found CB1 receptor up\u2010regulation in response to MPP<jats:sup>+<\/jats:sup>, lactacystin and paraquat and a protective effect of \u0394<jats:sup>9<\/jats:sup>\u2010THC against all three toxins. This neuroprotective effect was not reproduced by the CB1 receptor agonist WIN55,212\u20102 or blocked by the CB1 antagonist AM251. Furthermore, the antioxidants \u03b1\u2010tocopherol and butylhydroxytoluene as well as the antioxidant cannabinoids, nabilone and cannabidiol were unable to elicit the same neuroprotection as \u0394<jats:sup>9<\/jats:sup>\u2010THC. However, the peroxisome proliferator\u2010activated receptor\u2010gamma (PPAR\u03b3) antagonist T0070907 dose\u2010dependently blocked the neuroprotective, antioxidant and anti\u2010apoptotic effects of \u0394<jats:sup>9<\/jats:sup>\u2010THC, while the PPAR\u03b3 agonist pioglitazone resulted in protection from MPP<jats:sup>+<\/jats:sup>\u2010induced neurotoxicity. Furthermore, \u0394<jats:sup>9<\/jats:sup>\u2010THC increased PPAR\u03b3 expression in MPP<jats:sup>+<\/jats:sup>\u2010treated SH\u2010SY5Y cells, another indicator of PPAR\u03b3 activation. <jats:bold>Conclusions:<\/jats:bold> We have demonstrated up\u2010regulation of the CB1 receptor in direct response to neuronal injury in a human PD cell culture model, and a direct neuronal protective effect of \u0394<jats:sup>9<\/jats:sup>\u2010THC that may be mediated through PPAR\u03b3 activation.<\/jats:p>","DOI":"10.1111\/j.1365-2990.2011.01248.x","type":"journal-article","created":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T03:07:50Z","timestamp":1326337670000},"page":"535-547","source":"Crossref","is-referenced-by-count":90,"title":["\u0394<sup>9<\/sup>\u2010tetrahydrocannabinol (\u0394<sup>9<\/sup>\u2010THC) exerts a direct neuroprotective effect in a human cell culture model of Parkinson's disease"],"prefix":"10.1111","volume":"38","author":[{"given":"C. B.","family":"Carroll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.\u2010L.","family":"Zeissler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. O.","family":"Hanemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Zajicek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,17]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.09.011"},{"key":"e_1_2_8_3_2","first-page":"63","article-title":"CBD & \u03949\u2010THC \u2013 the two faces of cannabis","volume":"7","author":"Zeissler M\u2010L","year":"2010","journal-title":"Cell Sci Rev"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/346561a0"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/365061a0"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704327"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318198e0e9"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(02)00011-5"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000267407.79757.75"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2008.00088.x"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816x.2001.01812.x"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.03.009"},{"key":"e_1_2_8_13_2","first-page":"301","volume-title":"2nd Parkinsons Disease Symposium on Neurotoxic Factors in Parkinsons Disease and Related Disorders","author":"Lastres\u2010Becker I","year":"1999"},{"key":"e_1_2_8_14_2","doi-asserted-by":"crossref","unstructured":"Van LaereK CasteelsC LunskensS GoffinK GrachevID BormansG VandenbergheW.Regional changes in type 1 cannabinoid receptor availability in Parkinson's disease in vivo.Neurobiol Aging(in press). DOI:10.1016\/j.neurobiolaging.2011.02.009","DOI":"10.1016\/j.neurobiolaging.2011.02.009"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cnr.2005.08.015"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.11.009"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.11.063"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-007-0004-3"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35097089"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg224"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.03.011"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02065-1"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-08-02987.1999"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.54.3.459"},{"key":"e_1_2_8_25_2","doi-asserted-by":"crossref","first-page":"6475","DOI":"10.1523\/JNEUROSCI.21-17-06475.2001","article-title":"Neuroprotection by Delta(9)\u2010tetrahydrocannabinol, the main active compound in marijuana, against ouabain\u2010induced in vivo excitotoxicity","volume":"21","author":"van der Stelt M","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.78.1.43"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0233-y"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2009.04.017"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06764.x"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.03.017"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021525"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312497200"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2006.05.012"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287390701738467"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1080\/15287390500226987"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.05.150"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.03.102"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8268"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001560"},{"key":"e_1_2_8_40_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.042945"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.044412"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2004.07.012"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.064"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1998.70041366.x"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707423"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.09.121"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.095828"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.09.007"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06657.x"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2006.11.020"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02210.x"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00990.x"},{"key":"e_1_2_8_53_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcbr.2000.0176"},{"key":"e_1_2_8_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2008.11.003"},{"key":"e_1_2_8_55_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0768"},{"key":"e_1_2_8_56_2","first-page":"S258","article-title":"Peroxisome proliferator\u2010activated receptor gamma ligands alter endothelial NADPH oxidase activity and expression","volume":"51","author":"Calnek DS","year":"2003","journal-title":"J Investig Med"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0070"},{"key":"e_1_2_8_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2009.05.001"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.018911"}],"container-title":["Neuropathology and Applied Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2990.2011.01248.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2990.2011.01248.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T01:21:57Z","timestamp":1698628917000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2990.2011.01248.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,17]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1111\/j.1365-2990.2011.01248.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2990.2011.01248.x","archive":["Portico"],"relation":{},"ISSN":["0305-1846","1365-2990"],"issn-type":[{"value":"0305-1846","type":"print"},{"value":"1365-2990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,17]]}}}