Simultaneous measurement of monoamine metabolites and 5-methyltetrahydrofolate in the cerebrospinal fluid of children

Akiyama, Tomoyuki; Hayashi, Yumiko; Hanaoka, Yoshiyuki; Shibata, Takashi; Akiyama, Mari; Nakamura, Kazuyuki; Tsuyusaki, Yu; Kubota, Masaya; Yoshinaga, Harumi; Kobayashi, Katsuhiro

doi:10.1016/j.cca.2016.12.005

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…We described the clinical and biochemical profiles of nine Japanese patients with VB6- Reference values for HVA, MHPG, 5-HIAA, and 5-HTP are from Hyland et al [29]. We used modified reference values for 3-OMD based on our previous study [17].…”

Section: Discussionmentioning

confidence: 99%

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Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Akiyama

Hyodo

Hasegawa

et al. 2020

Pediatric Neurology

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Highlights Vitamin B6 (VB6) profiles in VB6-dependent epilepsy (ALDH7A1 and pyridoxal 5′phosphate [PLP] homeostasis protein deficiency) and other epilepsies were investigated.  In VB6-dependent epilepsy, concentrations of both PLP and pyridoxal (PL) in the cerebrospinal fluid were low whereas in the majority of other epilepsies with low PLP concentrations, PL concentrations were normal. Low PL concentrations in the cerebrospinal fluid may be a better indicator of VB6dependent epilepsy, particularly for PLP homeostasis protein deficiency, which currently lacks diagnostic metabolic biomarkers.

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Section: Discussionmentioning

confidence: 99%

“…We analyzed PLP, pyridoxal, and monoamine neurotransmitters according to previously reported methods [16,17] and a modified method for 5-hydroxytryptophan (5-HTP) after exclusion of known metabolic diseases that may affect AASA and PA concentrations.…”

Section: Assays Of Metabolitesmentioning

confidence: 99%

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Akiyama

Hyodo

Hasegawa

et al. 2020

Pediatric Neurology

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“…For PLP, an UHPLC-MS/MS approach has been published 23,24 , which allows the identification of seven vitamin B6 vitamers in human CSF samples, though this procedure is not routinely used for PLP quantification in biological fluids. Recently, a simultaneous measurement of monoamine metabolites and, also 5methyltetrahdyrofolate, in CSF by HPLC-FD has been developed 25 . Taking together, the methodological information stated in this work may be very helpful for both clinical and basic research laboratories.…”

Section: Comparison With Other Commonly Employed Methodsmentioning

confidence: 99%

Analysis of human cerebrospinal fluid monoamines and their cofactors by HPLC

Batllori¹,

Molero-Luís

Ormazábal

et al. 2017

Nat Protoc

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The presence of monoamines and their cofactors (the pterins and vitamin B (pyridoxal phosphate (PLP))) in human cerebrospinal fluid (CSF) can be used as indicators of the biosynthesis and turnover of dopamine and serotonin in the brain. In addition, abnormalities in the CSF levels of these molecules are associated with various neurological diseases, including genetic diseases leading to dopamine and serotonin deficiency. Here, we provide a set of quantitative high-performance liquid-chromatography (HPLC) approaches to determine CSF levels of monoamines and their cofactors. This protocol describes step-by-step procedures for CSF sample preparation for the analysis of different molecules, HPLC calibration and analysis, and data quantification and interpretation. Unlike plasma/tissue/blood samples, CSF requires minimal sample preparation: in this protocol, only the analysis of PLP requires mixing with trichloroacetic acid to release the protein-bound vitamin, centrifugation, and mixing of the supernatant with phosphate buffer and sodium cyanide for derivatization in alkaline conditions. Monoamines are analyzed by HPLC with coulometric electrochemical detection (ED), pterins are analyzed by HPLC with coupled coulometric electrochemical and fluorescence detection, and PLP is analyzed by HPLC with fluorescence detection. The quantification of all compounds is achieved by external calibration procedures, and internal quality control and standards are analyzed in each run. We anticipate that investigation of dopamine and serotonin disturbances will be facilitated by measurements of these compounds in human CSF and other biological samples. The estimated time for the different procedures primarily depends on the electrochemical detector stabilization. Overnight stabilization of this detector is advised, and, after that step, preanalytical equilibration rarely exceeds 3 h.

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“…It is uncertain whether the high variation in metabolite abundance was a reflection of ion suppression due to the CSF matrix, or indeed a limitation of the instrumentation utilised herein. Previous studies have utilised quantitative high pressure liquid chromatography with fluorescence or electrochemical detection [48,49] for the measurement of neurotransmitters. Furthermore, monoamine metabolites have been derivitised using benzylamine to improve analytical sensitivity [50].…”

Section: Figurementioning

confidence: 99%

Impact of Nitisinone on the Cerebrospinal Fluid Metabolome of a Murine Model of Alkaptonuria

et al. 2022

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Background: Nitisinone-induced hypertyrosinaemia is well documented in Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a decline in cognitive function and/or mood by altering neurotransmitter metabolism. The aim of this work was to evaluate the impact of nitisinone on the cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to providing additional insight into metabolic changes that occur following treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c Hgd−/− mice (n = 8, treated with nitisinone—4 mg/L and n = 9, no treatment). Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted feature extraction algorithm and an established in-house accurate mass retention time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 min retention time window) were filtered based on their frequency and variability. Experimental groups were compared using a moderated t-test with Benjamini–Hochberg false-discovery rate adjustment. Results: L-Tyrosine, N-acetyl-L-tyrosine, γ-glutamyl-L-tyrosine, p-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold change 2.6–6.9, 3/5 were significant p < 0.05) in the mice that received nitisinone. Several other metabolites of interest were matched, but no significant differences were observed, including the aromatic amino acids phenylalanine and tryptophan, and monoamine metabolites adrenaline, 3-methoxy-4-hydroxyphenylglycol, and octopamine. Conclusions: Evaluation of the CSF metabolome of a murine model of AKU revealed a significant increase in the abundance of a limited number of metabolites following treatment with nitisinone. Further work is required to understand the significance of these findings and the mechanisms by which the altered metabolite abundances occur.

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Simultaneous measurement of monoamine metabolites and 5-methyltetrahydrofolate in the cerebrospinal fluid of children

Cited by 9 publications

References 18 publications

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Analysis of human cerebrospinal fluid monoamines and their cofactors by HPLC

Impact of Nitisinone on the Cerebrospinal Fluid Metabolome of a Murine Model of Alkaptonuria

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