N-acetyl-aspartate: In-vitro expression in oligodendrocytes; implications for proton-MRS signal in vivo

Introduction N-acetyl-aspartate (NAA) is a major brain metabolite and its presence is used increasingly in clinical and experimental MRS studies as a putative neuronal marker. A reduction in NAA levels as assessed by in vim proton MRS has been suggested to be indicative of neuronal viability. However temporal observations of brain pathologies such as multiple sclerosis (MS), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS; 1) and hypothyroidism (2) have shown reversibility in NAA levels, possibly reflecting recovery of neuronal function. Knowledge of the cellular localisation of NAA is critical in interpreting these findings. The assumption that NAA is specific to neurons is based on previous immunohistochemical studies on whole brain using NAA specific antibodies. The neuronal localisation was further substantiated by cell culture experiments by Urenjak et al (who also observed its presence in the O-2A [oligodendrocyte-type-2 astrocyte] progenitors and immature oligodendrocytes, but not in the mature oligodendrocytes (3). More recently, studies on oligodendrocyte biology have revealed the requirement for trophic factors to promote the generation, maturation and survival of oligodendrocytes in vitro (5) In the present study we have used this new information to implement a more pertinent cell cultivation procedure and demonstrate that mature oligodendrocytes can express NAA in vifvo