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Retinoid transport in Human CSF
Author(s) -
Libien Jenny,
Blaner Willaim S,
Piantedosi Roseann
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a397-b
Subject(s) - transthyretin , retinol , retinoid , retinol binding protein , endocrinology , chemistry , medicine , retinoic acid , cerebrospinal fluid , biochemistry , biology , vitamin , gene
Retinoid signaling is involved in multiple processes in the adult brain, including adult neurogenesis and memory formation. In order to determine how the brain maintains retinoid sufficiency, we examined retinoid levels and retinoid transport mechanisms in postmortem human cerebrospinal fluid (CSF), serum, and brain. In CSF, a retinoic acid concentration of 2.9 ± 0.3 ng/ml (9.8 pmol/ml; n = 6) and retinol concentration of 7.9 ± 1.1 ng/ml (27.6 pmol/ml; n = 21) was measured by HPLC. In hippocampus, the concentration of retinoic acid was 2.7 ± 0.70 ng/g (9.0 pmol/g; n = 3). We hypothesized that the CSF delivers retinoids to brain tissue. In order to investigate the transport mechanism and binding proteins for retinol in the CSF, tracer amounts (1μCi, <1 ng) of [ 3 H]retinol were incubated with CSF or with serum and separated by FPLC. In the circulation, retinol is bound to retinol binding protein (RBP) in complex with tetrameric transthyretin (TTR). In serum, the [ 3 H]retinol eluted as a major peak with the RBP‐TTR complex and as a minor peak bound to RBP alone. However, in CSF, the [ 3 H]retinol eluted as a major peak bound to RBP alone. Incubation of purified human serum TTR with [ 3 H]retinol and serum resulted in formation of a [ 3 H]retinol‐RBP‐TTR complex, however purified TTR did not bind to [ 3 H]retinol‐RBP in CSF. This could be due to a modification in the structure and sequence of RBP or TTR in the CSF that prevents complex formation.