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The <i>N</i>-acetylaspartate network begins in neurons with <i>N</i>-acetylaspartate production catalyzed by aspartate <i>N</i>-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in <i>N</i>-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 <i>N</i>-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/<i>Nat8l</i> 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 <i>N</i>-acetylaspartate network. This study shows that reduced <i>N</i>-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger <i>N</i>-acetylaspartate network fragility. To reveal why <i>N</i>-acetylaspartate is reduced in this pathology, other processes should be considered.