@article{MTMT:2718517,
	title = {Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway},
	url = {https://m2.mtmt.hu/api/publication/2718517},
	author = {Tortoriello, G and Morris, CV and Alpár, Alán and Fuzik, J and Shirran, SL and Calvigioni, D and Keimpema, E and Botting, CH and Reinecke, K and Herdegen, T and Courtney, M and Hurd, YL and Harkany, T},
	doi = {10.1002/embj.201386035},
	journal-iso = {EMBO J},
	journal = {EMBO JOURNAL},
	volume = {33},
	unique-id = {2718517},
	issn = {0261-4189},
	abstract = {Children exposed in utero to cannabis present permanent neurobehavioral and cognitive impairments. Psychoactive constituents from Cannabis spp., particularly Δ9-tetrahydrocannabinol (THC), bind to cannabinoid receptors in the fetal brain. However, it is unknown whether THC can trigger a cannabinoid receptor-driven molecular cascade to disrupt neuronal specification. Here, we show that repeated THC exposure disrupts endocannabinoid signaling, particularly the temporal dynamics of CB1 cannabinoid receptor, to rewire the fetal cortical circuitry. By interrogating the THC-sensitive neuronal proteome we identify Superior Cervical Ganglion 10 (SCG10)/stathmin-2, a microtubule-binding protein in axons, as a substrate of altered neuronal connectivity. We find SCG10 mRNA and protein reduced in the hippocampus of midgestational human cannabis-exposed fetuses, defining SCG10 as the first cannabis-driven molecular effector in the developing cerebrum. CB1 cannabinoid receptor activation recruits c-Jun N-terminal kinases to phosphorylate SCG10, promoting its rapid degradation in situ in motile axons and microtubule stabilization. Thus, THC enables ectopic formation of filopodia and alters axon morphology. These data highlight the maintenance of cytoskeletal dynamics as a molecular target for cannabis, whose imbalance can limit the computational power of neuronal circuitries in affected offspring. © 2014 The Authors.},
	keywords = {Adult; Female; Male; NEURITE OUTGROWTH; hippocampus; ARTICLE; MOUSE; Brain Mapping; Cell Differentiation; priority journal; controlled study; nonhuman; animal experiment; fetus; PROTEIN FUNCTION; unclassified drug; cell structure; cannabinoid 1 receptor; brain development; protein degradation; nerve cell network; dronabinol; Marijuana; 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine; 1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n (1 piperidyl) 1h pyrazole 3 carboxamide; synaptogenesis; Growth cone; microtubule protein; Cannabis use; superior cervical ganglion 10 protein; stathmin 2 protein; axon},
	year = {2014},
	eissn = {1460-2075},
	pages = {668-685},
	orcid-numbers = {Alpár, Alán/0000-0003-4810-0820}
}

@article{MTMT:1120873,
	title = {Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain},
	url = {https://m2.mtmt.hu/api/publication/1120873},
	author = {Palkovits, Miklós and Harvey-White, J and Liu, J and Kovács, Zsolt and Bobest, M and Lovas, Gábor and Bagó, Attila György and Kunos, G},
	doi = {10.1016/j.neuroscience.2008.01.034},
	journal-iso = {NEUROSCIENCE},
	journal = {NEUROSCIENCE},
	volume = {152},
	unique-id = {1120873},
	issn = {0306-4522},
	abstract = {Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/in-line mass spectrometry. Measurements in brain samples stored at −80 °C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1–6 h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from 1 h after death, increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2-AG, which were 10–100 times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25–35% of the initial (‘0 min’) value, thereafter they remained relatively stable. As analyzed in samples removed 1–1.5 h postmortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain.},
	year = {2008},
	eissn = {1873-7544},
	pages = {1032-1039},
	orcid-numbers = {Palkovits, Miklós/0000-0003-0578-0387; Kovács, Zsolt/0000-0001-8571-5686}
}