Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the -Acetylaspartate Network in Wistar Rat Brain Cells.

The -acetylaspartate network begins in neurons with -acetylaspartate production catalyzed by aspartate -acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in -acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the -acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25-75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/ mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the -acetylaspartate network. This study shows that reduced -acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger -acetylaspartate network fragility. To reveal why -acetylaspartate is reduced in this pathology, other processes should be considered.