# Correlation of N-acetylaspartyl glutamate level in the medial prefrontal cortex with FTND and daily smoking amounts in adult cigarette smokers

**Authors:** Ke Xu, Miaomiao Yu, Liangjie Lin, Man Xu, Jianxin Ren, Qingqing Lv, Mengzhe Zhang, Shaoqiang Han, Weijian Wang, Jingliang Cheng, Yong Zhang

PMC · DOI: 10.3389/fnins.2025.1647427 · Frontiers in Neuroscience · 2025-10-06

## TL;DR

This study found that the level of a brain chemical called NAAG in smokers is linked to how much they smoke daily, suggesting a possible role in nicotine addiction.

## Contribution

The study is the first to show a correlation between NAAG levels in the medial prefrontal cortex and smoking behavior in adult smokers.

## Key findings

- NAAG levels in smokers correlated with daily smoking volume.
- NAAG/Cr levels were potentially correlated with the FTND score, a measure of nicotine dependence.
- No significant differences in other neurotransmitters like GABA or Glx were found between smokers and controls.

## Abstract

The neurotransmitter excitation/inhibition (E/I) balance is critical for maintaining normal brain function, and the contribution of nicotine signaling to homeostasis regulation and maintenance of E/I ratios is only beginning to be understood. Advanced J-edited 1H magnetic resonance spectroscopy (1H MRS) enables reliable detection of overlapped brain metabolite, including the neurotransmitters of glutamate (Glu) and N-acetylaspartyl glutamate (NAAG) and gamma-aminobutyric acid (GABA), etc. The purpose of this study was to explore the changes of neurotransmitters in the medial prefrontal cortex (mPFC) of smokers, so as to understand the potential metabolic mechanism of smoking addiction and make a contribution to the cause of smoking cessation.

In 2022, 45 males aged 40–60 years old were recruited. All subjects underwent routine magnetic resonance imaging (MRI) and the J-edited 1H MRS scans on a 3.0T MRI scanner. The edited spectra were post-processed and quantitatively analyzed using the Gannet tools. Two independent samples t-test was used to analyze the differences in GABA, glutamine/glutamic acid (Glx) and NAAG levels between nicotine addicts and control group; Finally, the spearman standard was used to analyze the correlation between metabolite levels and clinical characteristics assessment scales.

All measured metabolite levels in the brain mPFC region of smokers showed no significant difference to those of the control subjects. While the NAAG levels with reference to total creatine or water signals in smokers was significantly correlated with daily smoking volume, and the level of NAAG/Cr was potentially correlated with the FTND score.

In this study, we observed that the level of medial prefrontal NAAG in smokers was associated with daily smoking volume. This suggests that the metabolism of NAAG in the brain is related to nicotine, and the balance of glutaminergic system in the brain of smokers may be disrupted.

## Linked entities

- **Chemicals:** N-acetylaspartyl glutamate (PubChem CID 71120), glutamate (PubChem CID 611), gamma-aminobutyric acid (PubChem CID 119), glutamine (PubChem CID 738), creatinine (PubChem CID 588)

## Full-text entities

- **Diseases:** smoking addiction (MESH:D015208), nicotine addicts (MESH:D014029)
- **Chemicals:** N-acetylaspartyl glutamate (MESH:C027172), creatine (MESH:D003401), 1H (-), GABA (MESH:D005680), nicotine (MESH:D009538), Glu (MESH:D018698), water (MESH:D014867), Cr (MESH:D002857)
- **Mutations:** glutamine/glutamic acid

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12536034/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12536034/full.md

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Source: https://tomesphere.com/paper/PMC12536034