Evidence that lithium Inhibits Export of N-Acetyl-L-Aspartate from Neurons: A Retrospective Study of Canavan Disease and Bipolar Disorder Patients

Evidence that lithium Inhibits Export of N-Acetyl-L-Aspartate from Neurons: A Retrospective Study of Canavan Disease and Bipolar Disorder Patients

Lithium (Li) is an effective treatment for human bipolar disorder (BD) but whose precise mechanism and site of action are unknown. N-acetyl-L-aspartic acid (NAA) is an amino acid synthesized by and maintained at high steady-state levels within neurons from where it is exported to extracellular fluid (ECF) upon depolarization. NAA is the only precursor for N-acetylaspartylglutamate (NAAG), a neurotransmitter synthesized by neurons and also exported to ECF upon depolarization. The physiological function of NAA is as yet unclear but its unique tri-cellular metabolism between neurons, oligodendrocytes (NAA) and astrocytes (NAAG) is vital for normal brain function. Canavan disease (CD) is a rare inborn error in metabolism of NAA where oligodendrocyte aspartoacylase (ASPA) is inactive and NAA cannot be hydrolyzed resulting in its buildup in brain ECF and excretion in urine.