title: Assessment of cannabinoid induced gene changes: tolerance and neuroprotection.
abstract: The analysis of gene changes associated with exposure to cannabinoids is critical due to the multiple possible signaling pathways potentially affected by cannabinoid receptor activation. A comparison of altered gene profiles under two different conditions, one in vivo (chronic exposure to delta-9-THC) and the other in vitro (neuroprotection mediated by WIN55212-2), was made to determine whether it was possible to identify common genes that were affected. Up and down-regulated sets of genes are described. Genes affected in one or the other circumstance include alterations in a 14-3-3 regulator protein of PKC, CREB, BDNF and GABA receptor subunit proteins, as well as several genes associated with known cannabinoid receptor-coupled signaling pathways. Unexpectedly, several genes that were altered in both circumstances were associated with synaptic and membrane structure, motility and neuron growth. These included, neuronal cell adhesion molecule (NCAM), hyloronidan motility receptor, and myelin proteolipid protein. While the basis for involvement of these particular genes in cannabinoid receptor activated functional processes within the cell is still not well understood, awareness that significant numbers of genes and presumably proteins are changed following either acute or long-term exposure may provide new insight into their effects.
authors.affiliation: Millenium Pharmaceuticals Inc, Cambridge, MA, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Grigorenko
authors.forename: Joseph
authors.initials: J
authors.lastname: Kittler
authors.forename: Chris
authors.initials: C
authors.lastname: Clayton
authors.forename: Don
authors.initials: D
authors.lastname: Wallace
authors.forename: ShouYuan
authors.initials: S
authors.lastname: Zhuang
authors.forename: Daniel
authors.initials: D
authors.lastname: Bridges
authors.forename: Sarah
authors.initials: S
authors.lastname: Bundey
authors.forename: Andrew
authors.initials: A
authors.lastname: Boon
authors.forename: Clair
authors.initials: C
authors.lastname: Pagget
authors.forename: Seiji
authors.initials: S
authors.lastname: Hayashizaki
authors.forename: Gavin
authors.initials: G
authors.lastname: Lowe
authors.forename: Robert
authors.initials: R
authors.lastname: Hampson
authors.forename: Sam
authors.initials: S
authors.lastname: Deadwyler
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004361:Drug Tolerance; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D002186:Cannabinoids; D018076:DNA, Complementary; D018696:Neuroprotective Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014157:Transcription Factors; D019204:GTP-Binding Proteins