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)levels ofβ-phenylethylamine(PEA)。We measured CSF PEA levels in 17children with RS，in13 control children with no neurologic disease.CSF levels of PEA were also determined in patients with other age-matched neurological diseases including4patients with epilepsy and mental retardation and 5patients with autistic disorder.The l7RS children included9in stage II，7in stage III，and.1 in stage IV(mean age，52.7j±27.4months)。We also measured the CSF levels of homovanillic acid(HVA)，and 3-methoxy-4-hydroxy-phenylethylene glyco1(MHPG)using previously described methods.I D11，2个D1The extraction of PEA from CSF was performed by a method described previously.I D13文件D1The mean CSF level of PEA in patients with RS(287.2±j285.9pg/m1)was significantly lower than that of controls(936.2i±519.2pg/ml)，being31%of control values(p&lt；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，#china_person0#.1±7.7)and 1 patient with stage IV(age，137.0)were，187.5±158.7，417.0±387。1，276.3pg/ml，respectively。The CSF PEA levels in stage II were significantly lower than those of stage III(p&lt；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)。I D13锡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 nigra in-nine girls with RS.These findings may support the dysmaturation of dopaminergic neuron in RS I D 14 I D 1.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.I D15锡D1The link between this discovery and the alteration of CSF PEA should be clarified，especially during the early phase of disease onset。Less：Less

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