Pathophysiology of Rett syndrome-Can CSF phenyethylamine be a possible biological marker?-

To clarify the mechanism of brain impairment in Rett syndrome （RS）， we measured the cerebrospinal quid （CSF）。我们测量了17名患有RS的儿童的CSF PEA水平，13名患有无神经疾病的儿童PEA的CSF水平还确定了与其他年龄匹配的神经病学疾病，包括4名与癫痫和精神退化的患者和5名与自闭症患者。17 RS儿童包括第二阶段9，第三阶段7，第四阶段1（平均年龄， 52.7 j ± 27.4个月）。我们还使用先前描述的方法测量了聚乙烯酸（HVA）的CSF水平和3-methoxy-4-hydroxy-phenylene glyco 1（MHPG）的CSF水平。D1 The extraction of PEA from CSF was performed by a method described previously. D13 The mean CSF level of PEA in patients with RS（287.2 ± j 285.9 pg/m1）明显低于控制（936.2 i ± 519.2 pg/ml），控制值为31%（p < 0.05）。CSF PEA的水平 ... More the patients with stage II RS （n = 9） （age， 34.6 ± 9.2）， patients with stage III （n = 7） （age， 64.1 ± 7.7） and 1 patient with stage IV （age， 137.0） were ， 187.5 ± 158.7， 417.0 ± 387。1，276. 3 pg/ml， respectively。CSF PEA levels in stage II were significantly lower than those of stage III （p < 0.05）。PEA在儿童患有癫痫和精神退化的平均CSF水平，或自闭症与控制缺失的神经疾病没有明显的不同。在HVA和MHPG中，RS与那些控制中的CSF水平的平均值并不明显不同。最近，我们确定了在CSF中测量PEA水平的方法，在帕金森病中找到的CSF PEA水平低于年龄匹配的控制，在PEA和PD严重程度之间有明显的负相关性（Hoehn和Yahr阶段）。D13 Those results have strongly suggested that the CSF levels of PEA reflect the dopaminergic neuron degeneration in PD。我们目前的研究中最引人注目的发现是对CSF女孩与RS的PEA水平的显著减少。这是RS中PEA降级CSF级别的第一个演示。我们的研究还揭示了CSF水平或HVA和MHPG，多巴胺和北肾上腺素的代谢物并没有因患者而退化，神经病理学研究表明，黑色素含量在Substantia Nigra Zona Compacta中被明显降解，但在与RS的Substantia Nigra女孩的神经元中，没有差异。These findings may support the dysmaturation of dopaminergic neuron in RSイイD14イエD1。在我们的研究中发现的退化CSF PEA水平的显著性可能反映出对非性多巴胺神经元的影响的附加证据，因为PEA在这些神经元中合成。这是在PEA水平上最有趣的削减，因为在CSF最年轻的女孩与RS。在这一时期，疾病一次被注意到。这也可能是神经生物学水平的发育期。最近，MECP 2的变异，因为基因表达的表观规律有一个作用，在与RS的患者发现了这一发现之间的链接，CSF PEA应该是明确的，特别是在疾病早期阶段。Less（低）

To clarify the mechanism of brain impairment in Rett syndrome (RS), we measured the cerebrospinal quid (CSF) levels of β-phenylethylamine (PEA). We measured CSF PEA levels in 17 children with RS, in 13 control children with no neurologic disease. CSF levels of PEA were also determined in patients with other age-matched neurological diseases including 4 patients with epilepsy and mental retardation and 5 patients with autistic disorder. The l7 RS children included 9 in stage II, 7 in stage III, and.1 in stage IV ( mean age, 52.7 j ± 27.4 months). We also measured the CSF levels of homovanillic acid (HVA), and 3-methoxy-4-hydroxy-phenylethylene glyco1 (MHPG) using previously described methods.ィイD11 ,2ィエD1The extraction of PEA from CSF was performed by a method described previously.ィイD13ィエD1The mean CSF level of PEA in patients with RS (287.2 ± j285.9 pg/m1) was significantly lower than that of controls (936.2i ± 519.2 pg/ml), being 31% of control values (p < 0.05). The CSF PEA levels of … More the patients with stage II RS (n = 9) (age, 34.6 ± 9.2), patients with stage III (n = 7) (age, 64.1 ± 7.7) and 1 patient with stage IV (age, 137.0) were , 187.5 ± 158.7, 417.0 ± 387. 1, 276.3 pg/ml, respectively. The CSF PEA levels in stage II were significantly lower than those of stage III (p < 0.05). The mean CSF levels of PEA in children with epilepsy and mental retardation, or autistic disorder were not significantly different from controls lacking neurological disease. The mean CSF levels of HVA and MHPG in subjects with RS were not significantly different from those in controls.Recently, we established the methodology for measurement of PEA levels in CSF and found the CSF PEA level in Parkinson disease was lower than age-matched control, with a significant negative correlation between CSF level of PEA and PD severity (Hoehn and Yahr stage).ィイD13ィエD1 Those results have strongly suggested that the CSF levels of PEA reflect the dopaminergic neuron degeneration in PD. The most striking findings of our present studies are the marked reduction of PEA levels in CSF in girls with RS. This is the first demonstration of decreased CSF level of PEA in RS. Our study also revealed that CSF levels or HVA and MHPG, the metabolites of dopamine and norepinephrin are not decreased in patients with RS.Neuropathologic study has shown that melanin content is markedly decreased in substantia nigra zona compacta, but no difference in the number of neurons in the substantia nigra in-nine girls with RS. These findings may support the dysmaturation of dopaminergic neuron in RSィイD14ィエD1. The significance of decreased CSF PEA levels found in our study may reflect the additional evidence of the impairment of nigrostriatal dopaminergic neurons, because PEA was synthesized in these neurons. It is of interest that the most striking reduction in PEA levels in CSF occurred in the youngest girls with RS. It is during this period that disease onset is noted. This may also be the period of developmental arrest at the neurobiological level.Recently, mutations in MECP2, that has a role in a epigenetic regulation of gene expression, was discovered in patients with RS.ィイD15ィエD1 The link between this discovery and the alteration of CSF PEA should be clarified, especially during the early phase of disease onset. Less