新的研究表明許多被診斷患有精神分裂癥的患者——其中很大比例的患者不斷吸香煙——由于尼古丁對(duì)認(rèn)知功能的治療屬性而濫用煙草,。盡管已知尼古丁可以通過增加一種稱為谷氨酸脫羧酶67（GAD67）的蛋白質(zhì)功能從而影響大腦的化學(xué)性質(zhì)——精神分裂癥患者大腦中的這種蛋白質(zhì)異常偏低——它的準(zhǔn)確的機(jī)制尚不清楚,。
Rosalba Satta及其同事發(fā)現(xiàn)，不斷給小鼠皮下注射尼古丁會(huì)通過合成抑制性神經(jīng)遞質(zhì)γ-氨基丁酸（GABA）從而增加額葉的GAD67的表達(dá),。與正常人相比,，精神分裂癥患者的GABA含量減少,。這組作者證明了尼古丁通過提高額葉的上面兩層的GAD67從而增加了GABA的制造,。用一種能輕易穿過血腦屏障的藥物美加明預(yù)先治療小鼠,，這會(huì)阻斷尼古丁引起的GAD67表達(dá)增加。
這組科學(xué)家提出,，通過作用于氨基丁酸能神經(jīng)元上的煙堿型乙酰膽堿受體,，尼古丁增加了GAD67的表達(dá)，這可能有助于減輕精神分裂癥典型的幻覺,，精神分裂癥被認(rèn)為和氨基丁酸能神經(jīng)傳遞的缺乏有關(guān),。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS published October 13, 2008, doi:10.1073/pnas.0808699105
Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons
R. Satta, E. Maloku, A. Zhubi, F. Pibiri, M. Hajos, E. Costa, and A. Guidotti
Tobacco smoking is frequently abused by schizophrenia patients (SZP). The major synaptically active component inhaled from cigarettes is nicotine, hence the smoking habit of SZP may represent an attempt to use nicotine self-medication to correct (i) a central nervous system nicotinic acetylcholine receptor (nAChR) dysfunction, (ii) DNA-methyltransferase 1 (DMT1) overexpression in GABAergic neurons, and (iii) the down-regulation of reelin and GAD67 expression caused by the increase of DNMT1-mediated hypermethylation of promoters in GABAergic interneurons of the telencephalon. Nicotine (4.5–22 μmol/kg s.c., 4 injections during the 12-h light cycle for 4 days) decreases DNMT1 mRNA and protein and increases GAD67 expression in the mouse frontal cortex (FC). This nicotine-induced decrease of DNMT1 mRNA expression is greater (80%) in laser microdissected FC layer I GABAergic neurons than in the whole FC (40%), suggesting selectivity differences for the specific nicotinic receptor populations expressed in GABAergic neurons of different cortical layers. The down-regulation of DNMT1 expression induced by nicotine in the FC is also observed in the hippocampus but not in striatal GABAergic neurons. Furthermore, these data show that in the FC, the same doses of nicotine that decrease DNMT1 expression also (i) diminished the level of cytosine-5-methylation in the GAD67 promoter and (ii) prevented the methionine-induced hypermethylation of the same promoter. Pretreatment with mecamylamine (6 μmol/kg s.c.), an nAChR blocker that penetrates the blood–brain barrier, prevents the nicotine-induced decrease of FC DNMT1 expression. Taken together, these results suggest that nicotine, by activating nAChRs located on cortical or hippocampal GABAergic interneurons, can up-regulate GAD67 expression via an epigenetic mechanism. Nicotine is not effective in striatal medium spiny GABAergic neurons that primarily express muscarinic receptors.
