Department of Neuropsychiatry, Toho University Graduate School of Medicine, Tokyo, Japan.
Laboratory for Molecular Dynamics of Mental Disorders, Center for Brain Science, RIKEN, Wako-shi, Saitama, Japan.
Sci Rep. 2022 Jan 7;12(1):17. doi: 10.1038/s41598-021-03885-6.
Monoamine oxidase (MAO) is a key enzyme responsible for the degradation of neurotransmitters and trace amines. MAO has two subtypes (MAO-A and MAO-B) that are encoded by different genes. In the brain, MAO-B is highly expressed in the paraventricular thalamic nucleus (PVT); however, its substrate in PVT remains unclear. To identify the MAO-B substrate in PVT, we generated Maob knockout (KO) mice and measured five candidate substrates (i.e., noradrenaline, dopamine, 3-methoxytyramine, serotonin, and phenethylamine [PEA]) by liquid chromatography tandem mass spectrometry. We showed that only PEA levels were markedly elevated in the PVT of Maob KO mice. To exclude the influence of peripheral MAO-B deficiency, we developed brain-specific Maob KO mice, finding that PEA in the PVT was increased in brain-specific Maob KO mice, whereas the extent of PEA increase was less than that in global Maob KO mice. Given that plasma PEA levels were elevated in global KO mice, but not in brain-specific KO mice, and that PEA passes across the blood-brain barrier, the substantial accumulation of PEA in the PVT of Maob KO mice was likely due to the increase in plasma PEA. These data suggest that PEA is a substrate of MAO-B in the PVT as well as other tissues.
单胺氧化酶（MAO）是一种负责降解神经递质和痕量胺的关键酶。MAO 有两种亚型（MAO-A 和 MAO-B），它们由不同的基因编码。在大脑中，MAO-B 在室旁丘脑核（PVT）中高度表达；然而，其在 PVT 中的底物尚不清楚。为了确定 PVT 中的 MAO-B 底物，我们生成了 Maob 敲除（KO）小鼠，并通过液相色谱串联质谱法测量了五种候选底物（即去甲肾上腺素、多巴胺、3-甲氧基酪胺、血清素和苯乙胺[PEA]）。结果表明，只有 PEA 的水平在 Maob KO 小鼠的 PVT 中显著升高。为了排除外周 MAO-B 缺乏的影响，我们开发了大脑特异性 Maob KO 小鼠，发现大脑特异性 Maob KO 小鼠的 PVT 中 PEA 增加，而 PEA 增加的程度小于全脑 Maob KO 小鼠。鉴于全 KO 小鼠的血浆 PEA 水平升高，但脑特异性 KO 小鼠的血浆 PEA 水平没有升高，并且 PEA 可以穿过血脑屏障，因此 Maob KO 小鼠的 PVT 中 PEA 的大量积累可能是由于血浆 PEA 的增加所致。这些数据表明，PEA 是 PVT 以及其他组织中 MAO-B 的底物。
