Biosynthesis and Extracellular Concentrations of N, N-dimethyltryptamine (DMT) in Mammalian Brain
Biosynthesis and Extracellular Concentrations of N, N-dimethyltryptamine (DMT) in Mammalian Brain
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DOI：
10.1038/s41598-019-45812-w
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发表时间：
2019-06-27
影响因子：
4.6
通讯作者：
Borjigin, Jimo
中科院分区：
文献类型：
--
作者：
Dean, Jon G.;Liu, Tiecheng;Borjigin, Jimo
N，N-二甲基色胺（DMT）是一种内源性的致幻剂，由芳香族-L-氨基酸脱羧酶（AADC）和吲哚乙胺-N-甲基转移酶（INMT）生物合成。DMT是否在哺乳动物大脑中生物合成尚不清楚。我们研究了大鼠和人类中INMT转录物的脑表达，大鼠脑和外周中INMT和AADC mRNA的共表达，以及大鼠中DMT的脑浓度。通过原位杂交，在大鼠和人类的大脑皮质、松果体和脉络丛中鉴定了INMT转录本。值得注意的是，INMT mRNA与AADC转录物在大鼠脑组织中共定位，而在大鼠外周组织中INMT与AADC转录物几乎没有重叠表达。此外，在正常行为大鼠的大脑皮层中，有或没有松果体，DMT的细胞外浓度与包括5-羟色胺在内的典型单胺神经递质的浓度相似。在诱导实验性心脏骤停后，观察到大鼠视觉皮层中DMT水平显著增加，这一发现独立于完整的松果体。这些结果首次表明，大鼠大脑能够以与已知单胺神经递质相当的浓度合成和释放DMT，并提高了这种现象可能在人脑中类似地发生的可能性。
N, N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-Nmethyltransferase (INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.