Abstract
BackgroundIn humans, N-acetyl L-aspartate (NAA) has not been detected in other tissues than the brain. The physiological function of NAA is yet undefined. Recently, it has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation.Methodology and Principal FindingsUsing Gas Chromatography-Mass Spectrometry, we demonstrated that NAA was present in a high micromolar concentration in oCF of epithelial ovarian tumors (EOTs) of serous histology, sometimes in the same range as found in the extracellular space of the human brain. In contrast, oCF of EOTs with a mucinous, endometrioid and clear cell histological subtype contained a low micromolar concentration of NAA. Serous EOTs have a cellular differentiation pattern which resembles the lining of the fallopian tube and differs from the other histological subtypes. The NAA concentration in two samples of fluid accumulation in the fallopian tube (hydrosalpinx) was in the same ranges as NAA found in oCF of serous EOTs. The NAA concentration in oCF of patients with serous EOTs was mostly 10 to 50 fold higher than their normal serum NAA concentration, whereas in patients with other EOT subtypes, serum and cyst fluid NAA concentration was comparable.Conclusions and SignificanceThe high concentration of NAA in cyst fluid of serous EOTs and low serum concentrations of NAA in these patients, suggest a local production of NAA in serous EOTs. Our findings provide the first identification of NAA concentrations high enough to suggest local production outside the human brain. Our findings contribute to the ongoing research understanding the physiological function of NAA in the human body.
Highlights
N-acetyl L-aspartate (NAA) is the second most abundant free amino acid in the human brain.[1]
Our findings provide the first identification of NAA concentrations high enough to suggest local production outside the human brain
NAA in serous epithelial ovarian tumors (EOTs) was significantly higher compared to the other histological subtypes (p,0.001, Kruskal Wallis test)
Summary
N-acetyl L-aspartate (NAA) is the second most abundant free amino acid in the human brain.[1]. NAA is considered to be an intermediate in the formation of the neuropeptide N-acetylaspartylgutamate, a storage vehicle for neuronal aspartate and glutamate [1,2,3] Interestingly, a patient has been described with a biosynthesis defect of NAA. This patient had a severe neurological disorder with delayed myelination but was still alive at 8 years and 6 months of age.[4]. It has been suggested that NAA may function as a molecular water pump, responsible for the removal of large amounts of water from the human brain. Ovarian tumors typically present as large cystic masses with considerable fluid accumulation
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