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1.
J Cereb Blood Flow Metab ; 39(10): 2061-2073, 2019 10.
Article in English | MEDLINE | ID: mdl-29798726

ABSTRACT

Hydrocephalus (HC) is an imbalance in cerebrospinal fluid (CSF) secretion/absorption resulting in fluid accumulation within the brain with consequential pathophysiology. Our research has identified a unique cerebral folate system in which depletion of CSF 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is associated with cortical progenitor cell-cycle arrest in hydrocephalic Texas (H-Tx) rats. We used tissue culture, immunohistochemistry, in-situ PCR and RT-PCR and found that the in-vitro proliferation of arachnoid cells is highly folate-dependent with exacerbated proliferation occurring in hydrocephalic CSF that has low FDH but high folate-receptor-alpha (FRα) and folate. Adding FDH to this CSF prevented aberrant proliferation indicating a regulatory function of FDH on CSF folate concentration. Arachnoid cells have no detectable mRNA for FRα or FDH, but FDH mRNA is found in the choroid plexus (CP) and CSF microvesicles. Co-localization of FDH, FRα and folate suggests important functions of FDH in cerebral folate transport, buffering and function. In conclusion, abnormal CSF levels of FDH, FRα and folate inhibit cortical cell proliferation but allow uncontrolled arachnoid cell division that should increase fluid absorption by increasing the arachnoid although this fails in the hydrocephalic brain. FDH appears to buffer available folate to control arachnoid proliferation and function.


Subject(s)
Folic Acid/metabolism , Hydrocephalus/pathology , Animals , Arachnoid/cytology , Arachnoid/metabolism , Arachnoid/pathology , Cell Proliferation , Cells, Cultured , Female , Folate Receptor 1/cerebrospinal fluid , Folate Receptor 1/metabolism , Folic Acid/cerebrospinal fluid , Hydrocephalus/cerebrospinal fluid , Hydrocephalus/metabolism , Male , Oxidoreductases Acting on CH-NH Group Donors/cerebrospinal fluid , Oxidoreductases Acting on CH-NH Group Donors/metabolism , Rats , Rats, Sprague-Dawley
2.
Clin Chim Acta ; 465: 5-10, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27940130

ABSTRACT

BACKGROUND: We describe a new method for simultaneous measurement of monoamine metabolites (3-O-methyldopa [3-OMD], 3-methoxy-4-hydroxyphenylethyleneglycol [MHPG], 5-hydroxyindoleacetic acid [5-HIAA], and homovanillic acid [HVA]) and 5-methyltetrahydrofolate (5-MTHF) and its use on cerebrospinal fluid (CSF) samples from pediatric patients. METHODS: Monoamine metabolites and 5-MTHF were measured by high-performance liquid chromatography with fluorescence detection. CSF samples were prospectively collected from children according to a standardized collection protocol in which the first 1-ml fraction was used for analysis. RESULTS: Monoamine metabolites and 5-MTHF were separated within 10min. They showed linearity from the limit of detection to 1024nmol/l. The limit of quantification of each metabolite was sufficiently low for the CSF sample assay. In 42 CSF samples after excluding cases with possibly altered neurotransmitter profiles, the concentrations of 3-OMD, MHPG, 5-HIAA, HVA, and 5-MTHF showed significant age dependence and their ranges were comparable with the reference values in the literature. The metabolite profiles of aromatic l-amino acid decarboxylase deficiency, Segawa disease, and folate receptor α defect by this method were compatible with those in the literature. CONCLUSIONS: This method is a simple means of measuring CSF monoamine metabolites and 5-MTHF, and is especially useful for laboratories not equipped with electrochemical detectors.


Subject(s)
Dihydroxyphenylalanine/analogs & derivatives , Homovanillic Acid/cerebrospinal fluid , Hydroxyindoleacetic Acid/cerebrospinal fluid , Methoxyhydroxyphenylglycol/cerebrospinal fluid , Tetrahydrofolates/cerebrospinal fluid , Aromatic-L-Amino-Acid Decarboxylases/cerebrospinal fluid , Aromatic-L-Amino-Acid Decarboxylases/deficiency , Chromatography, High Pressure Liquid/methods , Dihydroxyphenylalanine/cerebrospinal fluid , Dystonic Disorders/cerebrospinal fluid , Fluorescence , Folate Receptor 1/cerebrospinal fluid , Folate Receptor 1/deficiency , Folate Receptor 1/genetics , Humans , Limit of Detection , Neuroaxonal Dystrophies/cerebrospinal fluid , Reference Values , Reproducibility of Results , Tyrosine/analogs & derivatives
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