Developmental Changes of N-Acetyl-Aspartyl-Glutamate (NAAG) in the Human Brain

Motivation: N-acetyl-aspartyl-glutamate (NAAG) is a dipeptide and glutamate neuromodulator with possible significance as therapeutical target for injuries and diseases associated with glutamate neurotoxicity. Goal(s): Determine age-dependent differences in its accumulation in white and grey matter in the human brain. Approach: Existing MR spectra from 410 “closest-to-normal” pediatric patients and controls were evaluated. Results: NAAG concentrations in the human brain were low and borderline detectable from birth to early childhood but then increased in late childhood in the parietal white matter whereas NAAG remained low in parietal grey matter. Impact: This study demonstrates that NAAG accumulates at late childhood predominantly in WM. Furthermore, it suggests that in vivo MRS can be used to assess NAAG levels in disorders associated with excessive glutamatergic neurotransmission, such as childhood seizures.